Testing the Coulomb/Accessible Surface Area solvent model for protein stability, ligand binding, and protein design

Background: Protein structure prediction and computational protein design require efficient yet sufficiently accurate descriptions of aqueous solvent. We continue to evaluate the performance of the Coulomb/Accessible Surface Area (CASA) implicit solvent model, in combination with the Charmm19 molecular mechanics force field. We test a set of model parameters optimized earlier, and we also carry out a new optimization in this work, using as a target a set of experimental stability changes for single point mutations of various proteins and peptides. The optimization procedure is general, and could be used with other force fields. The computation of stability changes requires a model for the unfolded state of the protein. In our approach, this state is represented by tripeptide structures of the sequence Ala-X-Ala for each amino acid type X. We followed an iterative optimization scheme which, at each cycle, optimizes the solvation parameters and a set of tripeptide structures for the unf...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Marcel Schmidt am Busch, Anne Lopes, Najette Amara, Christine Bathelt, Thomas Simonson
• Keywords: BMCBI 2008, Computational Protein Design, Protein, Stability Changes