VFFDT: A New Software for Preparing AMBER Force Field Parameters for Metal-Containing Molecular Systems

Force fields are fundamental to molecular dynamics simulations. However, the incompleteness of force field parameters has been a long-standing problem, especially for metal-related systems. In our previous work, we adopted the Seminario method based on the Hessian matrix to systematically derive the zinc-related force field parameters for AMBER. In this work, in order to further simplify the whole protocol, we have implemented a user-friendly Visual Force Field Derivation Toolkit (VFFDT) to derive the force field parameters via simply clicking on the bond or angle in the 3D viewer, and we have further extended our previous program to support the Hessian matrix output from a variety of quantum mechanics (QM) packages, including Gaussian 03/09, ORCA 3.0, QChem, GAMESS-US, and MOPAC 2009/2012. In this toolkit, a universal VFFDT XYZ file format containing the raw Hessian matrix is available for all of the QM packages, and an instant force field parametrization protocol based on a semiempirical quantum mechanics (SQM) method is introduced. The new function that can automatically obtain the relevant parameters for zinc, copper, iron, etc., which can be exported in AMBER Frcmod format, has been added. Furthermore, our VFFDT program can read and write files in AMBER Prepc, AMBER Frcmod, and AMBER Mol2 format and can also be used to customize, view, copy, and paste the force field parameters in the context of the 3D viewer, which provides utilities complementary to ANTECHAMBER, MCPB, and MCPB.py in the AmberTools.

[1]  Jian Zhang,et al.  Metal-coupled folding of Cys2His2 zinc-finger. , 2008, Journal of the American Chemical Society.

[2]  Alexander D. MacKerell,et al.  Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges , 2012, J. Chem. Inf. Model..

[3]  Carmay Lim,et al.  Zn protein simulations including charge transfer and local polarization effects. , 2005, Journal of the American Chemical Society.

[4]  G A Voth,et al.  Molecular dynamics simulations of human carbonic anhydrase II: Insight into experimental results and the role of solvation , 1998, Proteins.

[5]  Jorge M. Seminario,et al.  Harmonic Force Field for Glycine Oligopeptides , 2008 .

[6]  Pengfei Li,et al.  Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent. , 2013, Journal of chemical theory and computation.

[7]  J. Stewart.  Optimization of parameters for semiempirical methods V: Modification of NDDO approximations and application to 70 elements , 2007, Journal of molecular modeling.

[8]  Edson P Bellido,et al.  Harmonic force field for nitro compounds , 2011, Journal of Molecular Modeling.

[9]  James J. P. Stewart,et al.  Optimization of parameters for semiempirical methods VI: more modifications to the NDDO approximations and re-optimization of parameters , 2012, Journal of Molecular Modeling.

[10]  Kenneth M Merz,et al.  Structural Survey of Zinc Containing Proteins and the Development of the Zinc AMBER Force Field (ZAFF). , 2010, Journal of chemical theory and computation.

[11]  P. Kollman,et al.  Automatic atom type and bond type perception in molecular mechanical calculations. , 2006, Journal of molecular graphics & modelling.

[12]  Y. Pang,et al.  Successful molecular dynamics simulation of the zinc-bound farnesyltransferase using the cationic dummy atom approach. , 2000, Protein science : a publication of the Protein Society.

[13]  Toon Verstraelen,et al.  Automated Parametrization of AMBER Force Field Terms from Vibrational Analysis with a Focus on Functionalizing Dinuclear Zinc(II) Scaffolds. , 2012, Journal of chemical theory and computation.

[14]  Armando Rossello,et al.  Amber force field implementation, molecular modelling study, synthesis and MMP-1/MMP-2 inhibition profile of (R)- and (S)-N-hydroxy-2-(N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanamides. , 2006, Bioorganic & medicinal chemistry.

[15]  Pengfei Li,et al.  Parameterization of Highly Charged Metal Ions Using the 12-6-4 LJ-Type Nonbonded Model in Explicit Water , 2014, The journal of physical chemistry. B.

[16]  Jorge M. Seminario,et al.  Calculation of intramolecular force fields from second‐derivative tensors , 1996 .

[17]  Ray Luo,et al.  Molecular dynamics simulations of p53 DNA-binding domain. , 2007, The journal of physical chemistry. B.

[18]  K. Merz,et al.  Systematic Parameterization of Monovalent Ions Employing the Nonbonded Model. , 2015, Journal of chemical theory and computation.

[19]  K M Merz,et al.  Insights into the function of the zinc hydroxide-Thr199-Glu106 hydrogen bonding network in carbonic anhydrases. , 1990, Journal of molecular biology.

[20]  Ruibo Wu,et al.  A Transferable Non-bonded Pairwise Force Field to Model Zinc Interactions in Metalloproteins. , 2011, Journal of chemical theory and computation.

[21]  Peter A. Kollman,et al.  Application of the multimolecule and multiconformational RESP methodology to biopolymers: Charge derivation for DNA, RNA, and proteins , 1995, J. Comput. Chem..

[22]  K M Merz,et al.  Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from Bacillus cereus. , 2001, Journal of the American Chemical Society.

[23]  P A Kollman,et al.  Calculation and prediction of binding free energies for the matrix metalloproteinases. , 2000, Journal of medicinal chemistry.

[24]  Frank Neese,et al.  The ORCA program system , 2012 .

[25]  Ulf Ryde,et al.  Comparison of Methods to Obtain Force-Field Parameters for Metal Sites. , 2011, Journal of chemical theory and computation.

[26]  Pedro A Fernandes,et al.  Parameters for Molecular Dynamics Simulations of Manganese-Containing Metalloproteins. , 2013, Journal of chemical theory and computation.

[27]  Arthur J. Olson,et al.  AutoDock4Zn: An Improved AutoDock Force Field for Small-Molecule Docking to Zinc Metalloproteins , 2014, J. Chem. Inf. Model..

[28]  C. Lim,et al.  Empirical force fields for biologically active divalent metal cations in water. , 2006, The journal of physical chemistry. A.

[29]  Alexander D. MacKerell,et al.  Automation of the CHARMM General Force Field (CGenFF) I: Bond Perception and Atom Typing , 2012, J. Chem. Inf. Model..

[30]  John Z H Zhang,et al.  A New Quantum Calibrated Force Field for Zinc-Protein Complex. , 2013, Journal of chemical theory and computation.

[31]  Vincenzo Politi,et al.  Molecular dynamics simulation of Matrix Metalloproteinase 2: fluctuations and time evolution of recognition pockets , 2003, J. Comput. Aided Mol. Des..

[32]  Pengfei Li,et al.  MCPB.py: A Python Based Metal Center Parameter Builder , 2016, J. Chem. Inf. Model..

[33]  Renxiao Wang,et al.  Systematic Derivation of AMBER Force Field Parameters Applicable to Zinc-Containing Systems. , 2010, Journal of chemical theory and computation.

[34]  Lars Olsen,et al.  General Transition-State Force Field for Cytochrome P450 Hydroxylation. , 2007, Journal of chemical theory and computation.

[35]  M Karplus,et al.  Zinc binding in proteins and solution: A simple but accurate nonbonded representation , 1995, Proteins.

[36]  Mark S. Gordon,et al.  General atomic and molecular electronic structure system , 1993, J. Comput. Chem..

[37]  Yuan-Ping Pang,et al.  Novel Zinc Protein Molecular Dynamics Simulations: Steps Toward Antiangiogenesis for Cancer Treatment , 1999 .

[38]  Jon Baker,et al.  Q‐Chem 2.0: a high‐performance ab initio electronic structure program package , 2000, J. Comput. Chem..

[39]  Kristina Nilsson,et al.  An automatic method to generate force-field parameters for hetero-compounds. , 2003, Acta crystallographica. Section D, Biological crystallography.

[40]  Angelo Vedani,et al.  A new force field for modeling metalloproteins , 1990 .

[41]  Junmei Wang,et al.  Development and testing of a general amber force field , 2004, J. Comput. Chem..