George Dock: excerpts from the 34th Dock lecture.
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History, 19th Century↗
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Viscoelastic-Assisted Patient Interface Docking: A Technical Optimization in LenSx Femtosecond Laser-Assisted Cataract Surgery.
PURPOSE: To evaluate the efficacy of viscoelastic-assisted patient interface docking in LenSx (Alcon Laboratories, Inc) femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a randomized controlled trial. Patients undergoing FLACS from January to August 2025 at Aier Eye Hospital of Wuhan University were randomized via a random number table to receive balanced salt solution (BSS) or visoeleastic as the patient interface docking medium. The primary outcome was docking efficiency, measured by one-time docking success rate, the number of docking attempts, and mean docking time. Secondary outcomes included surgical safety (subconjunctival hemorrhage, capsulotomy completeness/tear rate), laser treatment duration (anterior capsulotomy time, nucleus pretreatment time, total laser emission time), and patient comfort (post-laser pain sensation). RESULTS: A total of 100 patients were enrolled, 50 in each group. Suction loss occurred in 7 patients (14%) in the BSS group and 1 patient (2%) in the viscoelastic group; the one-time docking success rate was significantly higher in the viscoelastic group (98%) than in the BSS group (86%) (chi-square = 3.93, P < .05). The viscoelastic group also had fewer mean docking attempts (1.02 ± 0.14) than the BSS group (1.16 ± 0.42), showing a significant difference (t = 2.23, P < .05). The viscoelastic group exhibited significantly shorter mean docking time (44.66 ± 4.47 seconds) compared to the BSS group (48.62 ± 3.11 seconds) (t = 2.17, P < .05). No significant differences were observed between the groups in subconjunctival hemorrhage, capsulotomy completeness/tear rate, anterior capsulotomy time, nucleus pretreatment time, total femtosecond laser emission time, or patient-reported pain sensation (all P > .05). CONCLUSIONS: Viscoelastic-assisted patient interface docking in FLACS effectively elevates one-time docking success rate, reduces docking attempts, and shortens docking time.
Humans↗
"Soft docking": matching of molecular surface cubes.
Molecular recognition is achieved through the complementarity of molecular surface structures and energetics with, most commonly, associated minor conformational changes. This complementarity can take many forms: charge-charge interaction, hydrogen bonding, van der Waals' interaction, and the size and shape of surfaces. We describe a method that exploits these features to predict the sites of interactions between two cognate molecules given their three-dimensional structures. We have developed a "cube representation" of molecular surface and volume which enables us not only to design a simple algorithm for a six-dimensional search but also to allow implicitly the effects of the conformational changes caused by complex formation. The present molecular docking procedure may be divided into two stages. The first is the selection of a population of complexes by geometric "soft docking", in which surface structures of two interacting molecules are matched with each other, allowing minor conformational changes implicitly, on the basis of complementarity in size and shape, close packing, and the absence of steric hindrance. The second is a screening process to identify a subpopulation with many favorable energetic interactions between the buried surface areas. Once the size of the subpopulation is small, one may further screen to find the correct complex based on other criteria or constraints obtained from biochemical, genetic, and theoretical studies, including visual inspection. We have tested the present method in two ways. First is a control test in which we docked the components of a molecular complex of known crystal structure available in the Protein Data Bank (PDB). Two molecular complexes were used: (1) a ternary complex of dihydrofolate reductase, NADPH and methotrexate (3DFR in PDB) and (2) a binary complex of trypsin and trypsin inhibitor (2PTC in PDB). The components of each complex were taken apart at an arbitrary relative orientation and then docked together again. The results show that the geometric docking alone is sufficient to determine the correct docking solutions in these ideal cases, and that the cube representation of the molecules does not degrade the docking process in the search for the correct solution. The second is the more realistic experiment in which we docked the crystal structures of uncomplexed molecules and then compared the structures of docked complexes with the crystal structures of the corresponding complexes. This is to test the capability of our method in accommodating the effects of the conformational changes in the binding sites of the molecules in docking.(ABSTRACT TRUNCATED AT 400 WORDS)
Antigen-Antibody Complex↗
Docking of chromaffin granules--a necessary step in exocytosis?
Putative docking of secretory vesicles comprising recognition of and attachment to future fusion sites in the plasma membrane has been investigated in chromaffin cells of the bovine adrenal medulla and in rat phaeochromocytoma (PC 12) cells. Upon permeabilization with digitonin, secretion can be stimulated in both cell types by increasing the free Ca2+-concentration to microM levels. Secretory activity can be elicited up to 1 hr after starting permeabilization and despite the loss of soluble cytoplasmic components indicating a stable attachment of granules to the plasma membrane awaiting the trigger for fusion. Docked granules can be observed in the electron microscope in permeabilized PC 12 cells which contain a large proportion of their granules aligned underneath the plasma membrane. The population of putatively docked granules in chromaffin cells cannot be as readily discerned due to the dispersal of granules throughout the cytoplasm. Further experiments comparing PC 12 and chromaffin cells suggest that active docking but not transport of granules can still be performed by permeabilized cells in the presence of Ca2+: a short (2 min) pulse of Ca2+ in PC 12 cells leads to the secretion of almost all releasable hormone over a 15 min observation period whereas, in chromaffin cells, with only a small proportion of granules docked, withdrawal of Ca2+ leads to an immediate halt in secretion. Transport of chromaffin granules from the Golgi to the plasma membrane docking sites seems to depend on a mechanism sensitive to permeabilization. This is shown by the difference in the amount of hormone released from the two permeabilized cell types, reflecting the contrast in the proportion of granules docked to the plasma membrane in PC 12 or chromaffin cells. Neither docking nor the docked state are influenced by cytochalasin B or colchicine. The permeabilized cell system is a valuable technique for the in vitro study of interaction between secretory vesicles and their target membrane.
Adrenal Gland Neoplasms↗
Secretory organelle docking at the cell membrane of Paramecium cells: dedocking and synchronized redocking of trichocysts.
We present the first evidence that secretory organelle docking at the cell membrane can be reversed in vivo. In nondischarge (nd) mutants of Paramecium tetraurelia all trichocysts can be detached from the cell surface within 2-3 h by different means, including cytochalasin B (but not D), high cell density, or Ca2+ ionophores. Considering the well-established ultrastructural differences between nd and wild-type (wt) cells, one can conclude that trichocyst docking at the cell periphery involves two docking sites (I, II): Site I ties the organelles to the epiplasm, and site II is the connection to the cell membrane at the fusogenic zone (expressed only in wt cells); both sites are close to the cell surface and only 150 nm apart. When the trigger for detachment of cortically docked trichocysts (high cell density, cytochalasin B) is relieved, trichocysts are synchronously reattached at the cell membrane, within 40-50 min, with a rate of 20-40 organelles/min, which far exceeds spontaneous docking rates. This is therefore also the first report on synchronization of secretory organelle docking. It is shown by radioactive leucine labeling that the same organelles are redocked, because trichocyst biogenesis is minimal under the conditions of de/redocking used. Surprisingly not only redocking but also detachment of trichocysts from the cell surface can be abolished by inhibitors of protein synthesis. Since Ca2+ ionophores mimic the effects of other conditions sufficient to detach trichocysts from the cell surface, we assume that a protein-dependent mechanism sensitive to Ca2+ (or other ions in exchange) may operate in trichocyst detachment. The precise mechanism involved in attachment or detachment of trichocysts remains to be elucidated.
Animals↗
Effects of local anesthesia and intravenous naloxone on the changes in behaviour and plasma concentrations of cortisol produced by castration and tail docking with tight rubber rings in young lambs.
The reliability of some behavioral and physiological indices used for the recognition and assessment of acute pain in lambs after castration and tail docking has been examined. Changes in the indices were measured after blocking neural activity with local anaesthetic (lignocaine) and after an opioid antagonist (naloxone) was administered. Six lambs, aged less than one week, were allocated randomly to each of six treatments. (i) control handling and blood sampling; (ii) castration plus tail docking with tight rubber rings; (iii) local anaesthesia; (iv) local anaesthesia followed by castration and tail docking; (v) intravenous naloxone only (0.2 mg kg-1); and (vi) intravenous naloxone followed by castration and tail docking. Local anaesthesia eliminated the behavioural and plasma cortisol changes which usually follow castration and tail docking. Naloxone had a limited effect on the increase in cortisol but altered the behaviour. The results support the view that such indices are useful for assessment of the response to acute pain and that, although endogenous opioids do reduce pain in young lambs after castration and tail docking, the effect is small.
Anesthesia, Local↗
A structural and functional analysis of the docking protein. Characterization of active domains by proteolysis and specific antibodies.
Docking protein is a 73-kDa integral membrane protein of the rough endoplasmic reticulum. It is essential for translocation of nascent secretory proteins into the lumen of the endoplasmic reticulum. Monoclonal and polyclonal antibodies have been generated which, in conjunction with limited proteolysis, have been used to characterize several subspecies of docking protein. These proteolytic fragments have been analyzed with respect to the various functions ascribed to docking protein which can be assayed in vitro. Proteolytic digestion of membrane-associated or of affinity-purified intact docking protein showed that: elastase cleavage generates a 59-kDa soluble fragment and one of 14 kDa which contains the membrane anchoring domain; trypsin as well as endogenous proteolysis generates a 46-kDa fragment, leaving a 27-kDa domain containing the membrane anchor. This 27-kDa fragment can be reduced to a 13- and a 14-kDa piece by elastase digestion. The characteristics of these various subspecies were examined. The 59-kDa soluble fragment, which can reconstitute full translocation activity to docking protein-depleted microsomes (Meyer, D. I., and Dobberstein, B. (1980) J. Cell Biol. 87, 503-508) was capable of releasing a signal recognition particle-mediated translation arrest. The 46-kDa fragment was neither able to reassociate with nor to reconstitute the activity of docking protein-depleted microsomes. Moreover this fragment was unable to release a signal recognition particle-mediated arrest. This suggests that the 13-kDa fragment (the difference between 46 and 59 kDa) is both essential for association with the membrane, and for the release of translation arrests.
Animals↗
New algorithm to model protein-protein recognition based on surface complementarity. Applications to antibody-antigen docking.
A novel algorithm is presented which models protein-protein interactions using surface complementarity. The method is applied to antibody-antigen docking. A steric scoring scheme, based upon a soft potential, is used to assess complementarity, and a simple electrostatic model is then used to remove infeasible interactions. The soft potential allows for structural changes that occur during docking. Biochemical knowledge is necessary to reduce the number of docking orientations produced by the method to a manageable size. The information used includes the known epitope residues and a single loose distance constraint. The method is applied to all three crystallographically determined antibody-lysozyme complexes, HyHEL-10, D1.3 and HyHEL-5. For the first time, a predicted antibody structure (that of D1.3) is used as a docking target. In the four systems modelled, the method identifies between 15 and 40 possible docking orientations. The root-mean-square (r.m.s.) deviation between these orientations and the relevant crystallographic complex is measured in the interface region. For all four complexes an orientation is found with r.m.s. deviation in the range 1.9 A and 4.8 A. The algorithm is implemented on a single instruction/multiple datastream (SI/MD) architecture computer. The use of a parallel architecture computer ensures detailed coverage of the search space, whilst still maintaining a search time of two days.
Algorithms↗
Homology of 54K protein of signal-recognition particle, docking protein and two E. coli proteins with putative GTP-binding domains.
Most proteins exported from mammalian cells contain a signal sequence which mediates targeting to and insertion into the membrane of the endoplasmic reticulum (ER). Involved in this process are the signal-recognition particle (SRP) and docking protein (DP), the receptor for SRP in the ER membrane. SRP interacts with the signal sequence on nascent polypeptide chains and retards their further elongation, which resumes only after interaction of the arrested ribosomal complex with the docking protein. SRP is a ribonucleoprotein particle comprising a 7S RNA and six polypeptides with relative molecular masses (Mr) of 9,000 (9K) 14K, 19K, 54K, 68K and 72K (ref. 1). The 9K and 14K proteins are essential for elongation arrest and the 68K-72K heterodimer is required for docking to the ER membrane. The 54K protein binds to the signal sequence when it emerges from the ribosome. Docking protein consists of two polypeptides, a 72K alpha-subunit (DP alpha) and a 30K beta-subunit (DP beta). No components structurally homologous to SRP and docking protein have yet been found in yeast or Escherichia coli. To understand the molecular nature of the interaction between the signal sequence and its receptor(s) we have characterized a complementary DNA coding for the 54K protein of SRP. Significant sequence homology was found to part of DP alpha and two E. coli proteins of unknown function. The homologous region includes a putative GTP-binding domain.
Amino Acid Sequence↗
Distance-constrained molecular docking by simulated annealing.
An optimized method based on the principle of simulated annealing is presented for determining the relative position and orientation of interacting molecules. The spatial relationships of these molecules are described by intermolecular distance constraints between specific pairs of atoms, such as found in hydrogen bonds or from experimentally determined data. The method makes use of a random walk through six rotational and translational degrees of freedom where the constituent molecules are treated as rigid bodies. Van der Waals repulsions are used only to define a lower bound on distances between constrained atom pairs within the docking procedure. A cost function comprised of purely geometric constraints is optimized via simulated annealing, in order to search for the best orientation and position of the two molecules. Our docking procedure is applied to eight serine proteinase complexes from the Brookhaven Protein Data Bank. For each simulation 100 computations were performed. A typical docking computation requires only a few seconds of CPU time on a VAXserver 3500. The influence of the number of constraints on the final docked positions was studied. The sensitivity of the docking procedure to a ligand structure which is not well defined is also addressed. Possible applications of this method include using approximate distances incorporating complete energy functions.
Aspartic Acid Endopeptidases↗
Investigating the molecular mechanism of Yangxin decoction in treating major depressive disorder using network pharmacology and molecular docking technology approaches.
Yangxin decoction has been used to treat major depressive disorder (MDD). This study aims to identify the active components and potential mechanisms of Yangxin decoction in treating MDD using network pharmacology and molecular docking technology. The active components and targets of Yangxin decoction were screened, and MDD-related targets were predicted. Networks of "herbal medicine-active components-potential targets" and protein-protein interaction were constructed. Core components and core targets were identified through network topology analysis. Gene ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on candidate genes. Molecular docking was conducted using AutoDock software (Olson Laboratory of the Scripps Research Institute, San Diego) to explore the interactions between core targets and active components, and the results were visualized using PyMOL (DeLano Scientific LLC, South San Francisco). A total of 433 active components and 392 targets of Yangxin decoction were identified, along with 11,796 MDD-related targets. There were 680 overlapping targets between Yangxin decoction and MDD, associated with 104 active components. Core targets identified through network topology analysis and molecular docking included serine/threonine kinase 1 (AKT1), tumor necrosis factor, interleukin-6, tumor protein P53, and proto-oncogene tyrosine-protein kinase Src. Gene ontology enrichment analysis revealed 1606 biological processes, 191 cellular components, and 373 molecular functions. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 212 signaling pathways, with significant enrichment in caffeine metabolism, bladder cancer, advanced glycation end products-receptor for advanced glycation end products signaling pathway in diabetic complications, and vascular endothelial growth factor signaling pathway. Molecular docking results showed strong binding energy between core active components and core targets. Yangxin decoction exhibits multi-component, multi-pathway, and multi-target therapeutic characteristics. It primarily regulates targets such as AKT1, tumor necrosis factor, interleukin-6, tumor protein P53, and proto-oncogene tyrosine-protein kinase Src through advanced glycation end products-receptor for advanced glycation end products, vascular endothelial growth factor, and ErbB signaling pathways, exerting anti-inflammatory, immune-regulating, and oxidative stress-inhibiting effects to alleviate MDD.
Molecular Docking Simulation↗
Analysis of the molecular mechanism underlying di(2-ethylhexyl) phthalate-induced bladder carcinogenesis via network toxicology and molecular docking approaches: An observational study.
This study aims to investigate the toxicity of di(2-ethylhexyl) phthalate (DEHP) and the potential molecular mechanisms of DEHP-induced bladder cancer (BLCA) using network toxicology and molecular docking strategies. The toxicity of DEHP was assessed using Prox-II software, and potential targets for DEHP-induced BLCA were identified by integrating data from ChEMBL database, Search Tool for Interactions of Chemicals, SwissTargetPrediction, GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas. STRING database and Cytoscape were employed to construct target networks and determine core targets. The expression levels of core targets were analyzed using R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on potential and core targets. Molecular docking was carried out using CB-Dock 2 to verify the interactions between DEHP and core targets. A total of 105 potential targets related to DEHP-induced BLCA were identified, from which 7 core targets were selected: cyclin-dependent kinase 1, interleukin 6, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, cyclin B2, and B-cell lymphoma 2. IL-6 and B-cell lymphoma 2 showed downregulated expression in tumor tissues, while cyclin-dependent kinase 1, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, and cyclin B2 were upregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these targets were enriched in cell signaling and cancer-related pathways. Molecular docking confirmed that DEHP interacts with these core targets. DEHP may promote the development of BLCA by interacting with key proteins and signaling pathways. This study provides a theoretical basis for understanding the molecular mechanisms of DEHP-induced BLCA and offers references for future prevention and treatment strategies.
Diethylhexyl Phthalate↗
Elucidating the Mechanism of Xiaoqinglong Decoction in Chronic Urticaria Treatment: An Integrated Approach of Network Pharmacology, Bioinformatics Analysis, Molecular Docking, and Molecular Dynamics Simulations.
INTRODUCTION: Xiaoqinglong Decoction (XQLD) is a traditional Chinese medicinal formula commonly used to treat chronic urticaria (CU). However, its underlying therapeutic mechanisms remain incompletely characterized. This study employed an integrated approach combining network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulations to identify the active components, potential targets, and related signaling pathways involved in XQLD's therapeutic action against CU, thereby providing a mechanistic foundation for its clinical application. METHODS: The active components of XQLD and their corresponding targets were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CU-related targets were retrieved from the OMIM and GeneCards databases. Subsequently, core components and targets were determined via protein-protein interaction (PPI) network analysis and component-target-pathway network construction. Topological analyses were performed using Cytoscape software to prioritize core nodes within these networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database to identify enriched biological processes and signaling pathways. Molecular docking was performed to evaluate binding interactions between key components and core targets, while molecular dynamics (MD) simulations were employed to assess the stability of the component-target complexes with the lowest binding energy. Finally, CU-related targets of XQLD were validated using datasets from the Gene Expression Omnibus (GEO) database. RESULTS: A total of 135 active components and 249 potential targets of XQLD were identified, alongside 1,711 CU-related targets. Core components, such as quercetin, kaempferol, beta-sitosterol, naringenin, stigmasterol, and luteolin, exhibited high degree values in the constructed networks. The core targets identified included AKT1, TNF, IL6, TP53, PTGS2, CASP3, BCL2, ESR1, PPARG, and MAPK3. GO and KEGG pathway enrichment analyses revealed the PI3K-Akt signaling pathway as a central regulatory mechanism. Molecular docking studies demonstrated strong binding affinities between active components and core targets, with the stigmasterol-AKT1 complex exhibiting the lowest binding energy (-11.4 kcal/mol) and high stability in MD simulations. Validation using GEO datasets identified 12 core genes shared between CU-related targets and XQLD-associated targets, including PTGS2 and IL6, which were also prioritized as core targets in the network pharmacology analyses. DISCUSSION: This study comprehensively integrates multidisciplinary approaches to clarify the potential molecular mechanisms of XQLD in treating CU, highlighting its multitarget and multipathway synergistic effects. Molecular docking and dynamics simulations confirm the stable interaction between stigmasterol and the core target AKT1. Additionally, GEO dataset analysis verifies the pathogenic relevance of targets such as PTGS2 and IL6, significantly enhancing the credibility of our findings. These results provide a modern scientific basis for the traditional therapeutic effects of XQLD on CU and have important implications for developing multitarget treatments for this condition. However, this study mainly relies on database mining and computational simulations. Further in vitro and in vivo experimental validations are needed to confirm the predicted component-target-pathway interactions. CONCLUSION: This study identifies the active components, potential targets, and pathways through which XQLD exerts therapeutic effects on CU. These findings provide a theoretical foundation for further mechanistic studies and support their clinical application in the treatment of CU.
Molecular Docking Simulation↗
A Network Pharmacology and Molecular Docking Study of TongBi Formula for Osteoarthritis.
This study applied network pharmacology combined with molecular docking to predict the potential therapeutic targets and molecular mechanisms of TongBi Formula (TBF) in osteoarthritis (OA). Active components and corresponding targets of TBF were retrieved from the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform, while OA-related targets were collected from Online Mendelian Inheritance in Man, GeneCards, DrugBank, and Therapeutic Target Database. A network visualization and analysis software was used to construct compound-target and protein-protein interaction (PPI) networks. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery platform. Molecular docking analysis was conducted using a molecular docking software to evaluate the predicted binding affinity between key active compounds and core target proteins. A total of 47 overlapping targets between TBF and OA were identified. PPI network analysis highlighted JUN, RELA, IL6, MAPK1, and IL10 as potential hub targets. Enrichment analysis suggested that TBF may regulate inflammation, lipid metabolism, and multiple intracellular signaling pathways associated with OA progression. Molecular docking results demonstrated favorable predicted binding affinities between core active compounds and key OA-related protein targets. These findings provide a computational framework for understanding the potential mechanisms of TBF against OA and support further experimental validation.
Molecular Docking Simulation↗
Integrated Network Pharmacology and Molecular Docking Analysis of Sishen Decoction Identifies Potential Targets and Pathways in Gout.
Gout is a disease characterized by hyperuricemia and the deposition of urate crystals in joints and soft tissues, leading to recurrent acute arthritis. Its increasing prevalence imposes substantial clinical and socioeconomic burdens. Sishen Decoction (SSD) has been used in the treatment of gout, but its potential molecular mechanisms remain unclear. This study applied an integrated network pharmacology and molecular docking approach to identify potential targets and signaling pathways associated with SSD in gout. Active compounds and corresponding targets of SSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while gout-related targets were collected from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Overlapping targets were identified and used to construct a drug-component-target-disease network. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking using the docking server analysis module. A total of 37 bioactive compounds were associated with 116 overlapping gout-related targets. The top hub targets included TP53, IL6, IL1B, TNF, AKT1, EGFR, CASP3, JUN, BCL2, and MMP9. GO analysis suggested that these targets are involved in gene expression regulation and signal transduction. KEGG enrichment analysis indicated significant associations with the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), interleukin-17 (IL-17), and tumor necrosis factor (TNF) signaling pathways. Molecular docking predicted favorable interactions between key compounds and hub targets, with all binding energies of ≤-5 kcal/mol. These computational findings provide potential mechanistic hypotheses for the action of SSD in gout and may support future experimental validation.
Molecular Docking Simulation↗
Docking by least-squares fitting of molecular surface patterns.
Molecular surfaces are fitted to each other by a new solution to the problem of docking a ligand into the active site of a protein molecule. The procedure constructs patterns of points on the surfaces and superimposes them upon each other using a least-squares best-fit algorithm. This brings the surfaces into contact and provides a direct measure of their local complementarity. The search over the ligand surface produces a large number of dockings, of which a small fraction having the best complementarity and the least steric hindrance are evaluated for electrostatic interaction energy. When applied to molecules taken from crystallographically observed complexes, this procedure consistently assigns the lowest electrostatic energies to correct dockings. On independently determined structures, the ability of the method to discern correct dockings depends on how much conformational difference there is between the free and complexed forms of the molecules. The procedure is found to be fast enough on contemporary workstation computers to permit many conformations to be considered, and tolerant enough to make rather coarse bond dihedral sampling a practicable way to overcome the problem of structural flexibility.
Binding Sites↗
Leptospiral and hepatitis A antibodies amongst windsurfers and waterskiers in Bristol City Docks.
Previous epidemiological studies have detected a substantial risk of gastroenteritis associated with snorkel swimming events in the Bristol City Docks. The event has since been discontinued. Similar risks were not identified at that time for surface-based events. A subsequent fatality from Weil's disease (Leptospirosis) and a case of Hepatitis A associated with surface water immersion in the Bristol City Docks water prompted this study of Leptospiral and Hepatitis A immunity amongst regular windsurfers and waterskiers. Although one person showed evidence of past Leptospiral infection and several people showed evidence of previous Hepatitis A, a causal association with Docks water exposure was not established. Nevertheless, there was sufficient public concern to justify the introduction of precautions against the potential health risks associated with immersion in the City Docks. The study findings and these preventive measures are described.
Adolescent↗
Stress responses in lambs docked and castrated surgically or by the application of rubber rings.
A comparative study has been made in lambs 3 to 6 weeks of age of the behavioural responses and changes in plasma immunoreactive beta-endorphin (ir beta-endorphin) and cortisol after docking or docking plus castration by the application of rubber rings or by surgery. The use of rubber rings on lambs at this age was characterised by very agitated behaviour indicative of considerable distress for a period of up to 1 h. In contrast, surgery was accompanied by some post-operative shock exhibited by reduced exploratory and social behaviour, at least in the lambs exposed to docking plus castration. In the latter group there were highly significant increases in both plasma ir beta-endorphin and cortisol concentrations that may be consistent with the induction of stress-induced analgesia. We conclude that surgery caused less distress than the rubber rings, and is therefore preferable for docking and castration of lambs 3 to 6 weeks of age.
Animals↗