Publication Category: Quantum Mechanics

  • A Variational Linear-Scaling Framework to Build Practical, Efficient Next-Generation Orbital-Based Quantum Force Fields

    J. Chem. Theory Comput. 2013, 9, 3, 1417–1427

    We introduce a new hybrid molecular orbital/density-functional modified divide-and-conquer (mDC) approach that allows the linear-scaling calculation of very large quantum systems. The method provides a powerful framework from which linear-scaling force fields for molecular simulations can be developed. The method is variational in the energy and has simple, analytic gradients and essentially no break-even point

  • On the Rational Design of Zeolite Clusters for Converging Reaction Barriers: Quantum Study of Aldol Kinetics Confined in HZSM-5

    J. Phys. Chem. C 2018, 122, 40, 23230–23241

    We have performed density functional theory calculations to investigate the convergence of reaction barriers with respect to zeolite cluster size, for multistep reactions catalyzed in HZSM-5. We constructed cluster models of HZSM-5 using the delta-cluster approach reported previously by us. We then computed barriers for different reaction types to determine the cluster sizes and neighbor-list

  • Improving Force Field Parameters for Small‐Molecule Conformation Generation

    Computational Pharmaceutical Solid State Chemistry, 57

    This chapter focuses on conformations of small molecules of the size of typical drug-like molecules (molecular weight <500 Da) with the aim of accurately predicting conformations, which could then be used as inputs for polymorph prediction programs. Physics-based molecular mechanics force fields are used to generate low-energy conformations, independent of the crystal packing environment, and

  • On the Rational Design of Zeolite Clusters

    ACS Catal. 2015, 5, 5, 2859–2865

    We have applied density functional theory calculations to systematically investigate zeolite cluster-size convergence for two acid-zeolite-catalyzed processes related to the conversion of biomass: (1) the keto–enol tautomerization of acetone in HZSM-5 and HY and (2) the protonation and ring opening of furan in HZSM-5. We have used these reactions as platforms to study two different

  • Close Intramolecular Sulfur–Oxygen Contacts: Modified Force Field Parameters for Improved Conformation Generation

    Journal of Computer-Aided Molecular Design volume 26, pages1195–1205(2012)

    The Cambridge Structural Database (CSD) offers an excellent data source to study small molecule conformations and molecular interactions. We have analyzed 130 small molecules from the CSD containing an intramolecular sulfur–oxygen distance less than the sum of their van der Waals (vdW) radii. Close S···O distances are observed in several important medicinal chemistry motifs (e.g.

  • Improving the Prediction of Absolute Solvation Free Energies Using the Next Generation OPLS Force Field

    J. Chem. Theory Comput. 2012, 8, 8, 2553–2558

    Explicit solvent molecular dynamics free energy perturbation simulations were performed to predict absolute solvation free energies of 239 diverse small molecules. We use OPLS2.0, the next generation OPLS force field, and compare the results with popular small molecule force fields—OPLS_2005, GAFF, and CHARMm-MSI. OPLS2.0 produces the best correlation with experimental data (R2 = 0.95, slope =

  • Prediction of Absolute Solvation Free Energies using Molecular Dynamics Free Energy Perturbation and the OPLS Force Field

    J. Chem. Theory Comput. 2010, 6, 5, 1509–1519

    Widely Cited

    The accurate prediction of protein−ligand binding free energies is a primary objective in computer-aided drug design. The solvation free energy of a small molecule provides a surrogate to the desolvation of the ligand in the thermodynamic process of protein−ligand binding. Here, we use explicit solvent molecular dynamics free energy perturbation to predict the absolute solvation