Identifying hot spots of inhibitor-CDK2 bindings by computational alanine scanning

Detecting hot interaction spots of inhibitors with Cyclin-dependent kinase 2 (CDK2) is required for design of clinical drugs toward CDK2. Molecular dynamics simulations (MDSs) and computational alanine scanning (CAS) method are integrated together to detect hot spots of DT1- and DT2-CDK2 associations. The results uncover that nine residues I10, V18, E81, L83, H84, Q85, K89, L134 and D145 are recognized as hot spots of inhibitor-CDK2 associations, which is in good consistence with the information revealed by calculations of residue-based free energy decomposition (RBFED). These nine residues can be used as potential targets of anti-cancer drug design targeting CDK2.