Physical and Theoretical Chemistry

Biography

Biography: Pavel Hobza

Abstract

Noncovalent interactions play an important role in chemistry, physics and biology. Reliable characteristics like stabilization energy, structure and vibrational frequencies are obtained using composite coupled cluster schemes which offer the possibility of improving the accuracy of results obtained by adding excitation operators of increasing order. It was shown that already CCSD(T)/ CBS method yields an accurate and reliable description of noncovalent interactions, yet is only applicable to systems with several tens of atoms. Lower-level methods like DFT or semiempieical QM (SQM) should be parametriezed or verified and here the databases of accurate stabilization energies and geometries developed in our laboratory (S22, S66, X40 and L7) play an indispensable role. Binding free energy for host-guest and protein-ligand complexes is constructed as a sum of gas-phase interaction energy (ΔEint), change of desolvation free-energy (ΔΔGsolv), change of the conformational free energy of both components (ΔGconfw) and entropy term (eq. 1): ΔGw ≈ ΔEint + ΔΔGsolv + ΔGconfw – TΔS (1). Because of the size of systems investigated the DFT-D, and PM6 or SCC-DF-TB SQM methods combined with COSMO technique were considered. Performance of these methods was verified by comparison of interaction energies of model complexes with the benchmark values obtained from CCSD(T) and MP2.5 methods. Applicability of procedures described is demonstrated for evaluation of binding free energies of several extended systems like host – guest, protein – ligand and surface – admolecule ones.