Quantum mechanical computations on very large molecular systems: The local self‐consistent field method

TLDR

Quantum chemical calculations on a subset of a large molecule can be performed at the NDDO level without further approximation if frontier atom orbitals are replaced by parametrized orthogonal hybrid orbitals. The method incorporates classical electrostatic interactions into SCF equations and analytically derives first and second energy derivatives, enabling energy minimization, transition state searches, and Newtonian dynamics. LSCF accurately reproduces proton transfer energetics in a tetrapeptide and a DHFR salt bridge, demonstrating that large systems with localized electronic changes can be simulated efficiently, making it valuable for biomolecular and surface reactivity studies. © 1994 John Wiley & Sons, Inc.

Abstract

Abstract Quantum chemical computations on a subset of a large molecule can be performed, at the neglect of diatomic differential overlap (NDDO) level, without further approximation provided that the atomic orbitals of the frontier atoms are replaced by parametrized orthogonal hybrid orbitals. The electrostatic interaction with the rest of the molecule, treated classically by the usual molecular mechanical approximations, is included into the self‐consistent field (SCF) equations. The first and second derivatives of energy are obtained analytically, allowing the search for energy minima and transition states as well as the resolution of Newton equations in molecular dynamics simulations. The local self‐consistent field (LSCF) method based on these approximations is tested by studying the intramolecular proton transfer in a Gly‐Arg‐Glu‐Gly model tetrapeptide, which reveals an excellent agreement between a computation performed on the whole molecule and the results obtained by the present method, especially if the quantum subsystem includes the side chains and the peptidic unit in between. The merits of the LSCF method are examplified by a study of proton transfer in the Asp 69 —Arg 71 salt bridge in dihydrofolate reductase. Simulations of large systems, involving local changes of electronic structure, are therefore possible at a good degree of approximation by introducing a quantum chemical part in molecular dynamics studies. This methodology is expected to be very useful for reactivity studies in biomolecules or at the surface of covalent solids. © 1994 by John Wiley & Sons, Inc.