Automated minimization of steric clashes in protein structures

作者：Ramachandran Srinivas; Kota Pradeep; Ding Feng; Dokholyan Nikolay V^*

来源：Proteins: Structure, Function, and Genetics , 2011, 79(1): 261-270.

DOI：10.1002/prot.22879

• homology modeling
• refinement
• Chiron
• discrete molecular dynamics
• protein design

Molecular modeling of proteins including homology modeling, structure determination, and knowledge-based protein design requires tools to evaluate and refine three-dimensional protein structures. Steric clash is one of the artifacts prevalent in low-resolution structures and homology models. Steric clashes arise due to the unnatural overlap of any two nonbonding atoms in a protein structure. Usually, removal of severe steric clashes in some structures is challenging since many existing refinement programs do not accept structures with severe steric clashes. Here, we present a quantitative approach of identifying steric clashes in proteins by defining clashes based on the Van der Waals repulsion energy of the clashing atoms. We also define a metric for quantitative estimation of the severity of clashes in proteins by performing statistical analysis of clashes in high-resolution protein structures. We describe a rapid, automated, and robust protocol, Chiron, which efficiently resolves severe clashes in low-resolution structures and homology models with minimal perturbation in the protein backbone. Benchmark studies highlight the efficiency and robustness of Chiron compared with other widely used methods. We provide Chiron as an automated web server to evaluate and resolve clashes in protein structures that can be further used for more accurate protein design. Proteins 2011; 79: 261-270.

• 出版日期2011-1