Biomedical subjects

Rosemary Braun

Publications and source records attributed to Rosemary Braun.

4 recordsLinked to original sources

PubMed2006

Imaging the migration pathways for O2, CO, NO, and Xe inside myoglobin.

Myoglobin (Mb) is perhaps the most studied protein, experimentally and theoretically. Despite the wealth of known details regarding the gas migration processes inside Mb, there exists no fully conclusive picture of these pathways. We address this deficiency by presenting a complete map of all the gas migration pathways inside Mb for small gas ligands (O2, NO, CO, and Xe). To accomplish this, we introduce a computational approach for studying gas migration, which we call implicit ligand sampling. Rather than simulating actual gas migration events, we infer the location of gas migration pathways based on a free-energy perturbation approach applied to simulations of Mb's dynamical fluctuations at equilibrium in the absence of ligand. The method provides complete three-dimensional maps of the potential of mean force of gas ligand placement anywhere inside a protein-solvent system. From such free-energy maps we identify each gas docking site, the pathways between these sites, to the heme and to the external solution. Our maps match previously known features of these pathways in Mb, but also point to the existence of additional exits from the protein matrix in regions that are not easily probed by experiment. We also compare the pathway maps of Mb for different gas ligands and for different animal species.

Carbon Monoxide↗

PubMed2005

Scalable molecular dynamics with NAMD.

NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Finally, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, for example, the Tcl scripting language. The article also provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu.

Algorithms↗

PubMed2004

Molecular Dynamics Simulations of Micelle Formation around Dimeric Glycophorin A Transmembrane Helices.

Insertion and formation of membrane proteins involves the interaction of protein helices with one another in lipid environments. Researchers have studied glycophorin A (GpA) transmembrane helices embedded in sodium dodecyl sulfate (SDS) micelles to identify contacts significant for helix dimerization. However, a detailed picture of the conformation and dynamics of the GpA-SDS system cannot be obtained solely through experiment. Molecular dynamics simulations of SDS and a GpA dimer can provide an atomic-level picture of SDS aggregation and helix association. We report 2.5-ns simulations of GpA wild-type and mutants in a preformed micelle as well as a 32-ns simulation showing the formation of a complete micelle around wild-type GpA from an initially random placement of SDS molecules in an aqueous environment. In the latter case, an initial instability of GpA helices in water is reversed after the helices become surrounded by SDS. The properties of the spontaneously formed micelle surrounding the GpA are indistinguishable from those of the preformed micelle surrounding the GpA dimer.

Amino Acid Substitution↗

PubMed2002

Genetically engineered gold-binding polypeptides: structure prediction and molecular dynamics.

The biological control of inorganic crystal formation, morphology, and assembly is of interest to biologists and biotechnologists studying hard tissue growth and regeneration, as well as to materials scientists using biomimetic approaches for the control of inorganic material fabrication and assembly. Biomimetics requires an accurate understanding of natural mechanisms at the molecular level. Such understanding can be derived from the use of metal surfaces to study surface recognition by proteins together with combinatorial genetics techniques for the selection of suitable peptides. Polymerization of these peptides produces engineered polypeptides large enough to encode their own folding information with low structural complexity, while enhancing binding affinity to surfaces. The low complexity of such polypeptides can aid in analyses, leading to modeling and eventual manipulation of the structure of the folded polypeptide. This paper presents structure predictions for gold-binding protein sequences, originally selected by combinatorial techniques. Molecular dynamics simulations lasting 5 ns were carried out using solvated polypeptides at the gold surface to assess the dynamics of the binding process and the effects of surface topography on the specificity of protein binding.

Amino Acid Sequence↗