A QM/MM Implementation of the Self-Consistent Charge Density Functional Tight Binding (SCC-DFTB) Method

Abstract

A quantum mechanical/molecular mechanical (QM/MM) approach based on an approximate density functional theory, the so-called self-consistent charge density functional tight binding (SCC-DFTB) method, has been implemented in the CHARMM program and tested on a number of systems of biological interest. In the gas phase, SCC-DFTB gives reliable energetics for models of the triosephosphate isomerase (TIM) catalyzed reactions. The rms errors in the energetics compared to B3LYP/6-31+G(d,p) are about 2−4 kcal/mol; this is to be contrasted with AM1, where the corresponding errors are 9−11 kcal/mol. The method also gives accurate vibrational frequencies. For the TIM reactions in the presence of the enzyme, the overall SCC-DFTB/CHARMM results are in somewhat worse agreement with the B3LYP/6-31+G(d,p)/CHARMM values; the rms error in the energies is 5.4 kcal/mol. Single-point B3LYP/CHARMM energies at the SCC-DFTB/CHARMM optimized structures were found to be very similar to the full B3LYP/CHARMM values. The relative stabilities of the αR and 310 conformations of penta- and octaalanine peptides were studied with minimization and molecular dynamics simulations in vacuum and in solution. Although CHARMM and SCC-DFTB give qualitative different results in the gas phase (the latter is in approximate agreement with previous B3LYP calculations), similar behavior was found in aqueous solution simulations with CHARMM and SCC-DFTB/CHARMM. The 310 conformation was not found to be stable, and converted to the αR form in about 15 ps. The αR conformation was stable in the simulation with both SCC-DFTB/CHARMM and CHARMM. The i,i+3 CO···HN distances in the αR conformation were shorter with the SCC-DFTB method (2.58 Å) than with CHARMM (3.13 Å). With SCC-DFTB/CHARMM, significant populations with i,i+3 CO···HN distances near 2.25 Å, particularly for the residues at the termini, were found. This can be related to the conclusion from NMR spectroscopy that the 310 configuration contributes for alanine-rich peptides, especially at the termini.

Simulating Water with the Self-Consistent-Charge Density Functional Tight Binding Method: From Molecular Clusters to the Liquid State

“…In both the (H 2 O) 18 and (H 2 O) 10 clusters, it seems there is a tendency of forming three/four-member ring structure of water molecules in the SCCDFTB method, which partially explains the extra stabilization of the lowest-SCCDFTB-energy structures identified here.…”

“…For the (H 2 O) 18 cluster, the lowest-energy structures from two methods are shown in Fig 7. The biggest difference is the relative position of the two water molecules on the top: in the SCCDFTB structure, the two top water molecules formed a closed "basket handle" and resembled the SCCDFTB structure of (H 2 O) 10 cluster; in the HF/6-31G(d,p) structure, the two water molecules only interacted with an edge of the stacked water cubes. In both the (H 2 O) 18 and (H 2 O) 10 clusters, it seems there is a tendency of forming three/four-member ring structure of water molecules in the SCCDFTB method, which partially explains the extra stabilization of the lowest-SCCDFTB-energy structures identified here.…”

“…CPK model in red (oxygen) and white (hydrogen) is the structure minimized from the Cambridge Cluster Database; CPK model in blue is the lowest-energy conformation identified with the SCCDFTB method. Minimized structures of the (H 2 O) 18 cluster. CPK model in red (oxygen) and white (hydrogen) is the structure minimized from the Cambridge Cluster Database; CPK model in blue is the lowest-energy conformation identified with the SCCDFTB method.…”

Implementation of the SCC-DFTB Method for Hybrid QM/MM Simulations within the Amber Molecular Dynamics Package

“…Recent experimental results suggest that the backbone preferences in proteins are already present in blocked aminoacids. 55,56 A number of experimental 55,[57][58][59][60] and theoretical, [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] studies indicate that the potential energy surface for AD in vacuum and in solution are considerably different: While in the gas-phase the global minimum is believed to be a C7 eq structure (ϕ− 83°, ψ~73°), 70 interaction with water favors the polyproline-II (P II , (ϕ~−75°, ψ~150°) conformation. 60 AD has also been used previously to investigate the performance of the SCC-DFTB method as compared to different classical force fields.…”

Accelerating QM/MM Free Energy Calculations: Representing the Surroundings by an Updated Mean Charge Distribution

“…Here the obvious alternative is to evaluate the polarization by using the averaged potential from the solvent. This can be done by adding the solvent averaged potential to the solute Hamiltonian which in the simplest semiempirical formulation will look like 29, 30 : (11) where F is the Fock matrix. However, in the ab initio code the corresponding treatment is more complicated.…”