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B Robson

Publications and source records attributed to B Robson.

At least 55 records · Page 3Linked to original sources
PubMed1987

Comparative conformation-activity relationships for hormonally- and centrally-acting TRH analogues.

Empirical energy calculations have been applied to a series of thyrotrophin-releasing hormone (TRH) analogues in an attempt to incorporate the conformational parameter into traditional Quantitative Structure-Activity Relationships (QSAR). A search was made of the potential surface of each analogue using a SIMPLEX technique coupled with a model representing solvent effects as a dielectric continuum. Conformers of TRH can be described in terms of the distance between the pyroglutamyl, imidazole and prolyl rings, and presented as two-dimensional descriptor coordinates using multidimensional scaling. This process was repeated for stable and metastable conformers of all the TRH analogues investigated and correlated with experimental data on receptor affinity, relative stability and biological potency of the analogues. The results obtained suggest that modifications to the TRH structure can lead to greater potency in addition to improved stability, and that providing the appropriate theoretical approach is taken, it is possible to apply QSAR-based design procedures to conformationally-flexible drugs.

Animals↗
PubMed1986

Calculation of the conformation of glycosphingolipids. 2. GM1- and GM2-gangliosides.

The conformations of GM1- and GM2-gangliosides have been predicted by energy minimization techniques including an orbital force field approach. The global energy minimum conformers for these two gangliosides show marked differences, particularly in the relative orientation of the sugar rings. The predicted structures are compared with those postulated from NMR spectroscopy in relation to the formation of a cation-binding site. The minimum energy conformer of GM2-ganglioside is able to form this binding site whereas this conformer of GM1-ganglioside is not. The nature of the specific interaction of gangliosides with activator proteins is discussed.

Carbohydrate Conformation↗
PubMed1986

An algorithm for secondary structure determination in proteins based on sequence similarity.

A secondary structure prediction algorithm is proposed on the hypothesis that short homologous sequences of amino acids have the same secondary structure tendencies. Comparisons are made with the secondary structure assignments of Kabsch and Sander from X-ray data [(1983) Biopolymers 22, 2577-2637] and an empirically determined similarity matrix which assigns a sequence similarity score between any two sequences of 7 residues in length. This similarity matrix differs in many respects from that of the Dayhoff substitution matrix [(1978) in: Atlas of Protein Sequence and Structure, (Dayhoff, M.O. ed). vol. 5. suppl. 3, pp. 353-358, National Biochemical Research Foundation, Washington, DC]. This homologue method had a prediction accuracy of 62.2% over 3 states for 61 proteins and 63.6% for a new set of 7 proteins not in the original data base.

Amino Acid Sequence↗
PubMed1986

Refined models for computer calculations in protein engineering. Calibration and testing of atomic potential functions compatible with more efficient calculations.

A reappraisal has been made of interatomic potential functions for protein structure calculations using the all-atom approximation (except CH, CH2 and CH3, which are treated as "united atoms"). Some key problems are identified and treated. The potential functions are somewhat novel in form and consistent with more efficient and robust folding algorithms. In addition, the potentials are calibrated for for the rigid geometry approximation, since use of fixed standard bond lengths and valence angles (and fixed trans planar peptide groups) reduces the number of conformational variables and saves a great deal of computer time. Though these algorithms demand the use of potential functions of this special type, these functions can be readily implemented in more classical programs for the conformational analysis of proteins. They are calibrated or tested against a large body of experimental data, including extended basis set ab initio, quantum mechanical calculations, nuclear magnetic resonance spectroscopic data and dipole moment data for di- and oligopeptides, characteristic ratio data for random coil homopolypeptides, extensive data from peptide solubility studies, and experimental structures of polyalanine fibres and globular proteins. This paper will form the basis of a further report, which will include investigations of how water might be more realistically represented subject to the computing power available.

Amino Acid Sequence↗
PubMed1986

Calculation of the conformation of glycosphingolipids. 1. Beta-D-glucosyl-N-(2-D-hydroxyoctadecanoyl)-D-dihydrosphingosine (glucosyl-ceramide) and alpha-D-N-acetylneuraminyl-(2----3)-beta-D-galactose.

The conformation of a glucosyl-ceramide, beta-D-galactosyl-N-(2-D-hydroxyoctadecanoyl)-D-dihydrosphingos in e, and of the disaccharide, N-acetylneuraminyl-galactose have been predicted by energy minimization techniques including an orbital force field approach. The predictions have been shown to be in excellent agreement with the results of X-ray single crystal analysis and structures postulated from nuclear magnetic resonance methods and have confirmed the utility of the computational approach to the study of glycosphingolipids.

Carbohydrate Conformation↗
PubMed1986

Conformational study of thyrotrophin-releasing hormone. I. Aspects of importance in the design of novel TRH analogues.

The solution conformations of thyrotrophin-releasing hormone (TRH), a biologically-active tripeptide, have been predicted computationally using a method which represents solution effects as a dielectric continuum surrounding the molecule throughout energy minimisation; this is described as the reaction field contribution. The predicted conformations have been compared with previous experimental and theoretical studies. Favoured conformations of TRH under other simulated conditions have also been examined, including the behaviour of the cis isomer, and have been related to possible interactions with intermediates and with specific receptors. The relevance of these predictions to the design of biologically-active analogues of TRH has been analysed.

Hydrogen-Ion Concentration↗
PubMed1985

Prediction of the conformation and antigenic determinants of the V-sis viral oncogene product homologous with human platelet-derived growth factor.

In an extensive study involving unification of secondary structure prediction methods to predict peptide backbone angles, folding simulations, and interactive graphics we have calculated conformations for a 160 residue p28sis protein fragment. We demonstrate that the state of the art is sufficient to aid artificial vaccine design.

Antigens, Viral↗
PubMed1985

Marital adjustment and fatherhood.

This paper examines the relationship between marital stability and fathers' bonding to their first born infants. Current literature reports on the significant and unique influence of the father on his developing infant and the influence of the father on the mother-infant bond. Some authors suggest that prematurity, the type of delivery, or a father's presence or absence at the birth, influences his engrossment or bonding and later caretaking behaviour. However, little attention has been given to other factors such as the father's personality, education, previous experience with child care or his relationship with his spouse. Similarily, there is a paucity of research on the effect of the birth of the infant on the marital bond. Einzig, Wente and Crockenberg and Dyer suggest that the transition to parenthood is a crisis in the family life and can lead to disruption in the husband-wife relationship. With the apparent increase in family instability in the last decade as marked by the rising divorce rate, it seems crucial to explore what correlation, if any, exists between marital condition and a father's relationship to his newborn infant.

Adult↗
PubMed1983

The design of biologically active polypeptides.

On the one hand considerable advances are being made in the computer-aided calculation of polypeptide structure and behaviour, while on the other even very simple reasoning has lead to some apparent successes in the design and synthesis of biologically active peptides. While this looks extremely promising, there is a case for arguing that progress made in both these areas is to some degree illusory. Such criticisms as can be made, however, turn out to be highly constructive, suggesting a profitable and still workable approach to the problem of rational polypeptide design.

Animals↗
PubMed1980

Monte Carlo simulation of water behavior around the dipeptide N-acetylalanyl-N-methylamide.

Applications of Monte Carlo and molecular dynamics computer simulation techniques indicate that they are potentially powerful tools for understanding biological systems at the molecular level. The Monte Carlo technique can be used to study the solvent structure around a small peptide and the effect of the aqueous environment on the conformational equilibria of the peptide.

Alanine↗