Inventi Impact: Molecular Modeling

Inventi:pmm/16035/15

A QM-MD Simulation Approach to the Analysis of FRET Processes in (Bio)Molecular Systems. A Case Study: Complexes of E. coli Purine Nucleoside Phosphorylase and its Mutants with Formycin A

Predicting FRET pathways in proteins using computer\nsimulation techniques is very important for reliable interpretation\nof experimental data. A novel and relatively simple\nmethodology has been developed and applied to purine\nnucleoside phosphorylase (PNP) complexed with a fluorescent\nligand � formycin A (FA). FRET occurs between an\nexcited Tyr residue (D*) and FA (A). This study aims to interpret\nexperimental data that, among others, suggests the absence\nof FRET for the PNPF159A mutant in complex with\nFA, based on novel theoretical methodology. MD simulations\nfor the protein molecule containing D*, and complexed with\nA, are carried out. Interactions of D* with its molecular environment\nare accounted by including changes of the ESP\ncharges in S1, compared to S0, and computed at the SCF-CI\nlevel. FRET probability WF depends on the inverse six-power\nof the D*-A distance, Rda. The orientational factor 0