The SH3 domain is a molelcule found throughout many diverse biological systems. It is usually part of a larger complex that helps to integrate a cellular signals. Its main function is modulate and regulate signaling by transiently binding a certain class of polyproline motifs. The specificty of different forms of SH3 for certain peptide motifs can vary widely, and great insights into celluar signaling networks could be gained by computational prediction of sequence-dependent affiities.
These are simulations designed to test a new sampling method that we have been developing, called the multi-scale fragment potential (MSFP) method. In MSFP, the problem of computing how a peptide chain binds to a receptor surface is broken down into parts that can be efficiently parallelized. Instead of simulating the interaction between a large polypeptide chain and a receptor, we break the peptide chain into small fragments, and exhaustively scan the receptor surface to construct a potential of mean force for each fragment. Using this detailed chemical information, we then use a coarse-grained chain model to sample peptide conformation and sequence space.
The simulations in these projects are of single-amino fragments anchored along the surface of test protein, Abl SH3 domain. These tests will let us test some of the fundamental assumptions of the MSFP method.
List of Contributors
This project is managed by Prof. Vincent Voelz at Temple University.
Dr. Voelz's research focuses on using new simulation methods to unravel the mysteries of how proteins self-assemble into their functional folds, and to design folding and binding properties of proteins and peptide mimetics from first principles. The Voelz Lab participates in the Folding@home project, hosting two servers at Temple University. Dr. Voelz was formerly a postdoctoral scholar in the Vijay Pande lab at Stanford University.
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