Milan Hodošček

Bio: Milan Hodošček is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Ab initio & QM/MM. The author has an hindex of 20, co-authored 64 publications receiving 7599 citations. Previous affiliations of Milan Hodošček include Center for Information Technology.

CHARMM: the biomolecular simulation program.

Abstract: CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

Interfacing Q‐Chem and CHARMM to perform QM/MM reaction path calculations

Abstract: A hybrid quantum mechanical/molecular mechanical (QM/MM) potential energy function with Hartree-Fock, density functional theory (DFT), and post-HF (RIMP2, MP2, CCSD) capability has been implemented in the CHARMM and Q-Chem software packages In addition, we have modified CHARMM and Q-Chem to take advantage of the newly introduced replica path and the nudged elastic band methods, which are powerful techniques for studying reaction pathways in a highly parallel (ie, parallel/parallel) fashion, with each pathway point being distributed to a different node of a large cluster To test our implementation, a series of systems were studied and comparisons were made to both full QM calculations and previous QM/MM studies and experiments For instance, the differences between HF, DFT, MP2, and CCSD QM/MM calculations of H2O···H2O, H2O···Na+, and H2O···Cl− complexes have been explored Furthermore, the recently implemented polarizable Drude water model was used to make comparisons to the popular TIP3P and TIP4P water models for doing QM/MM calculations We have also computed the energetic profile of the chorismate mutase catalyzed Claisen rearrangement at various QM/MM levels of theory and have compared the results with previous studies Our best estimate for the activation energy is 820 kcal/mol and for the reaction energy is −231 kcal/mol, both calculated at the MP2/6-31+G(d)//MP2/6-31+G(d)/C22 level of theory © 2007 Wiley Periodicals, Inc J Comput Chem, 2007

Enzyme mechanisms with hybrid quantum and molecular mechanical potentials.i. theoretical considerations

Abstract: The application of hybrid quantum mechanical and molecular mechanical (QM/MM) potentials to the study of chemical reactions in enzymes is outlined. The discussion is general and addresses the difficulties encountered in an enzyme QM/MM study. First, general criteria for determining whether a particular enzyme is an appropriate candidate for a QM/MM approach are outlined. Methods for obtaining starting structures are detailed. The importance of choosing appropriate levels of ab initio or semiempirical theory is emphasized. Approaches for interfacing the QM and MM regions are briefly discussed, with greater detail given to describing our CHARMM-GAMESS interface. Techniques for partitioning the system into QM and MM regions are explored. Link atom placement, as distant from reacting atoms as possible within the confines of computational efficiency, is examined in some detail. Methods for determining reaction paths are also discussed. © 1996 John Wiley & Sons, Inc.

Optimization of quantum mechanical molecular mechanical partitioning schemes: Gaussian delocalization of molecular mechanical charges and the double link atom method

Abstract: Two new techniques for modeling chemical processes in condensed phases with combined quantum mechanical and molecular mechanical (QM/MM) potentials are introduced and tested on small, model compounds. The first technique, the double link atom (DLA) method, is an extension of the traditional, single link atom (SLA) method to avoid some of the problems with the latter method. These problems are primarily electrostatic, as the SLA method can produce an unphysical overall charge or dipole. The second technique, the delocalized Gaussian MM charge (DGMM) method, is an empirical way to include the delocalized character of the electron density of atoms in the MM region. This can be important for the electrostatic interaction of the QM region with nearby atoms in the MM region, and it can simplify the rules governing which classical interactions are included in the energies and forces. Even for very short distances, the DGMM method does not require the neglect of the MM host in the QM calculation. The DGMM method can be used for modeling reactions in solution, and it can be combined with methods such as the link atom, frozen orbital, or pseudopotential methods for terminating the QM region at a covalent bond. The DLA and the DGMM methods have been combined effectively. Presented here are tests on small, model systems that mimic properties important for reactions in proteins, in particular rotational barriers, proton affinities, and deprotonation energies. The new methods yield improved energetics for model compounds, vis-a-vis a point-MM-charge and SLA treatment.

CHARMMing: A new, flexible, web portal for CHARMM

Abstract: A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation, and dynamics). The infrastructure used to implement the web application is described. Two additional programs have been developed and integrated with CHARMMing: GENRTF, which is employed to define structural features not supported by the standard CHARMM force field, and a job broker, which is used to provide a portable method for using grid and cluster computing with CHARMMing. The use of the program is described with three proteins: 1YJP , 1O1O , and 1UFY . Source code is provided allowing CHARMMing to be downloaded, installed, and used by supercomputing centers and research groups that have a CHARMM license. Although no software can replace a scientist's own judgment and experience, CHARMMing eases the introduction of newcomers to the molecular modeling discipline by providing a graphical method for running simulations.

Quantum mechanical continuum solvation models.

Abstract: 6.2.2. Definition of Effective Properties 3064 6.3. Response Properties to Magnetic Fields 3066 6.3.1. Nuclear Shielding 3066 6.3.2. Indirect Spin−Spin Coupling 3067 6.3.3. EPR Parameters 3068 6.4. Properties of Chiral Systems 3069 6.4.1. Electronic Circular Dichroism (ECD) 3069 6.4.2. Optical Rotation (OR) 3069 6.4.3. VCD and VROA 3070 7. Continuum and Discrete Models 3071 7.1. Continuum Methods within MD and MC Simulations 3072

CHARMM: the biomolecular simulation program.

Abstract: CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Abstract: To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

Gromacs 4.5

Abstract: Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. Availability: GROMACS is an open source and free software available from http://www.gromacs.org. Contact: erik.lindahl@scilifelab.se Supplementary information:Supplementary data are available at Bioinformatics online.

CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.

Abstract: The widely used CHARMM additive all-atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug-like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug-like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present article in the context of the model systems, pyrrolidine, and 3-phenoxymethylpyrrolidine will allow users to readily extend the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform "all-CHARMM" simulations on drug-target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems.