Biomedical subjects

Brandon Hespenheide

Publications and source records attributed to Brandon Hespenheide.

3 recordsLinked to original sources

PubMed2006

The Database of Macromolecular Motions: new features added at the decade mark.

The database of molecular motions, MolMovDB (http://molmovdb.org), has been in existence for the past decade. It classifies macromolecular motions and provides tools to interpolate between two conformations (the Morph Server) and predict possible motions in a single structure. In 2005, we expanded the services offered on MolMovDB. In particular, we further developed the Morph Server to produce improved interpolations between two submitted structures. We added support for multiple chains to the original adiabatic mapping interpolation, allowing the analysis of subunit motions. We also added the option of using FRODA interpolation, which allows for more complex pathways, potentially overcoming steric barriers. We added an interface to a hinge prediction service, which acts on single structures and predicts likely residue points for flexibility. We developed tools to relate such points of flexibility in a structure to particular key residue positions, i.e. active sites or highly conserved positions. Lastly, we began relating our motion classification scheme to function using descriptions from the Gene Ontology Consortium.

Databases, Protein↗

PubMed2005

Constrained geometric simulation of diffusive motion in proteins.

We describe a new computational method, FRODA (framework rigidity optimized dynamic algorithm), for exploring the internal mobility of proteins. The rigid regions in the protein are first determined, and then replaced by ghost templates which are used to guide the movements of the atoms in the protein. Using random moves, the available conformational phase space of a 100 residue protein can be well explored in approximately 10-100 min of computer time using a single processor. All of the covalent, hydrophobic and hydrogen bond constraints are maintained, and van der Waals overlaps are avoided, throughout the simulation. We illustrate the results of a FRODA simulation on barnase, and show that good agreement is obtained with nuclear magnetic resonance experiments. We additionally show how FRODA can be used to find a pathway from one conformation to another. This directed dynamics is illustrated with the protein dihydrofolate reductase.

Algorithms↗

PubMed2005

Protein flexibility using constraints from molecular dynamics simulations.

Proteins are held together in the native state by hydrophobic interactions, hydrogen bonds and interactions with the surrounding water, whose strength as well as spatial and temporal distribution affects protein flexibility and hence function. We study these effects using 10 ns molecular dynamics simulations of pure water and of two proteins, the glutamate receptor ligand binding domain and barnase. We find that most of the noncovalent interactions flicker on and off over typically nanoseconds, and so we can obtain good statistics from the molecular dynamics simulations. Based on this information, a topological network of rigid bonds corresponding to a protein structure with covalent and noncovalent bonds is constructed, with account being taken of the influence of the flickering hydrogen bonds. We define the duty cycle for the noncovalent interactions as the percentage of time a given interaction is present, which we use as an input to investigate flexibility/rigidity patterns, in the algorithm FIRST which constructs and analyses topological networks.

Algorithms↗