Force fields protein-ligand interactions

Another approach based on statistical analysis of residue-specific protein-ligand interaction terms is named TScore [138[. Here, individual protein-ligand interactions are evaluated for each residue within 8 A around the ligand. Force field-based descriptors are replaced by Chemscore [96] and PLP [139] terms for hydrogen bonds, lipophilicity, and steric contact. Its application to a series of factor Xa inhibitors resulted in a predictive tailored scoring function vdth 52 selected descriptors after PLS analysis q = 0.(>4, r = 0.83). This concept allows a visual interpretation of... 

In a similar fashion, Catana and Stouten [143] developed multiple functions based on QXP protein-ligand interaction terms [112]. The concept was also applied for improving a force field-based scoring function for CDK-2 using short MD simulations based on quantum-refined force fields [144]. Here, the statistical analysis of... 

Force fields were originally developed to simulate the conformational, thermodynamic and kinetic behaviors of small molecules or macromolecules much more efficiently, from a computer resource perspective, than quantum mechanical methods. It was hoped that if the interaction components of the force fields were applied to docking and scoring, the more accurate representation of the physics of protein ligand interactions would result in more accurate predictions of protein ligand binding affinities. 

Maple, J. R., et al, A polarizable force field and continuum solvation methodology for modeling of protein-ligand interactions. /. Chem. Theor. Comput, 2005.1(4), 694-715. 

Pengyu Ren is associate professor of biomedical engineering and William J. Murray Jr. Fellow in Engineering No. 4 at the University of Texas at Austin, USA. His research interests include protein-ligand interaction, nucleic acid structure, and force field development. 

---