MCM Group

Software MCM

This page has links for webservers and software downloads provided by the Molecular and Cellular Modeling (MCM) group at the Heidelberg Institute for Theoretical Studies (HITS). There are tutorials for some software on our tutorials page. For queries, send email to: mcmsoft@h-its.org

LIGDIG

LigDig: a web server for querying ligand–protein interactions

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SYCAMORE

SYstems biology’s Computational Analysis and MOdeling Research Environment

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TRAPP

Tool for analysis of transient binding pockets in proteins

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PIPSA

Webserver (and software download) for comparing electrostatic potentials (or other molecular interaction fields) of protein structures

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SDA

Simulation of Diffusional Association – Brownian Dynamics Software

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webSDA

Webserver for Simulation of Diffusional Association

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L-RIP and RIPlig

Two non-equilibrium MD approaches for the identification of slow conformational changes of a protein binding site

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Molsurfer

Tool to link a 2D projection of a macromolecular interface to a 3D view of the macromolecular structures

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ProSAT+

Display protein annotations on protein structures.

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KBbox

KBbox is a toolbox of computational methods for studying the kinetics of molecular binding. It also provides an updated list of examples of published work for these methods, along with detailed tutorials to guide less experienced researchers.

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RAMD

The Random Acceleration Molecular Dynamics (RAMD) method can be used to carry out molecular dynamics simulations with an additional randomly oriented force applied to the center of mass of one molecule in the system. It can, for example, be used to identify egress routes for a ligand from a buried protein binding site.

We initially implemented RAMD in the ARGOS program (Luedemann et al, 2000), and have subsequently implemented it in AMBER8 and NAMD. There are implementations by other groups in other codes (see below).

RAMD implementations from the MCM group

RAMD and its applications (using the implementation in NAMD) are described in:

  • Kokh DB et. al. Estimation of Drug-Target Residence Times by τ-Random Acceleration Molecular Dynamics Simulations. J. Chem. Theory Comput.2018; DOI: 10.1021/acs.jctc.8b00230
  • Niu, Y., Li, S., Pan, D., Liu, H., Yao, X. Computational Study on the Unbinding Pathways of B-RAF Inhibitors and Its Implication for the Difference of Residence Time: Insight from Random Acceleration and Steered Molecular Dynamics Simulations. Phys. Chem. Chem. Phys. 2016, 18 (7),5622– 5629, DOI: 10.1039/C5CP06257H
  • Xiaofeng Yu, Prajwal Nandekar, Ghulam Mustafa, Vlad Cojocaru, Galina I. Lepesheva and Rebecca C. Wade. Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design. Biochim. Biophys. Acta (BBA) – General Subjects , (2016) 1860:67-78, DOI: 10.1016/j.bbagen.2015.10.015
  • Vlad Cojocaru, Peter J. Winn and Rebecca C. Wade, Multiple, Ligand-dependent Routes from the Active Site of Cytochrome P450 2C9. Curr. Drug. Metab. (2012) 13:143-154, DOI: 10.2174/138920012798918462
  • Vashisth, H., Abrams, C.F. Ligand escape pathways and (un)binding free energy calculations for the hexameric insulin-phenol complex. Biophys. J. 95, 4193-4204 (2008).DOI:10.1529/biophysj.108.139675

RAMD and its applications (using the implementation in AMBER unless otherwise specified) are described in:

  • Lüdemann SK, Carugo O, Wade RC. Substrate access to cytochrome P450cam: a comparison of a thermal motion pathway analysis with molecular dynamics simulation data. J. Mol. Model. (1997) 3, 369-374. DOI:10.1007/s008940050053 (Initial ARGOS implementation)
  • Luedemann, S.K., Lounnas, V. and R. C. Wade. How do Substrates Enter and Products Exit the Buried Active Site of Cytochrome P450cam ? 1. Random Expulsion Molecular Dynamics Investigation of Ligand Access Channels and Mechanisms. J Mol Biol, 303:797-811 (2000). doi:10.1002/jmbi.2000.4154 (First description of method and implementation in ARGOS)
  • Luedemann, S.K., Gabdoulline,R.R., Lounnas, V. and R. C. Wade. Substrate access to cytochrome P450cam investigated by molecular dynamics simulations: An interactive look at the underlying mechanisms. Internet Journal of Chemistry, 4, 6 (2001). http://www.ijc.com/articles/2001v4/6/ (using the ARGOS implementation)
  • Winn,P., Luedemann, S.K., Gauges,R., Lounnas, V. and R. C. Wade. Comparison of the dynamics of substrate access channels in three cytochrome P450s reveals different opening mechanisms and a new functional role for a buried arginine PNAS, 99, 5361-5366 (2002). Full text (using the ARGOS implementation)
  • Schleinkofer, K., Sudarko, Winn,P., Luedemann, S.K. and R. C. Wade. Do mammalian cytochrome P450s show multiple ligand access pathways and ligand channelling? EMBO Reports, 6, 584-589 (2005).doi:10.1038/sj.embor.7400420
  • Carlsson, P., Burendahl, S., Nilsson, L. Unbinding of retinoic acid from the retinoic acid receptor by random expulsion molecular dynamics. Biophys. J. 91, 3151-3161 (2006).doi:10.1529/biophysj.106.082917 (Implementation in CHARMM)
  • Wang, T., Duan, Y. Chromophore channeling in the G-protein coupled receptor rhodopsin. J. Am. Chem. Soc. 129, 6970-6971 (2007).doi:10.1021/ja0691977
  • Long, D., Mu, Y. Yang, D. Molecular Dynamics Simulation of Ligand Dissociation from Liver Fatty Acid Binding Protein. PLoS ONE 4, e6801 (2008).doi:10.1371/journal.pone.0006081 (Implementation of a variant of RAMD in GROMACS)
  • Perakyla, M. Ligand unbinding pathways from the vitamin D receptor studied by molecular dynamics simulations. 38, 185-198 (2009).doi:10.1007/s00249-008-0369-x
  • Klvana, M. et al. Pathways and Mechanisms for Product Release in the Engineered Haloalkane Dehalogenases Explored Using Classical and Random Acceleration Molecular Dynamics Simulations J. Mol. Biol. 392, 1339-1356 (2009).doi:10.1016/j.jmb.2009.06.076
  • Pavlova, M. et al. Redesigning dehalogenase access tunnels as a strategy for degrading an anthropogenic substrate Nature Chem. Biol. 5, 727-733 (2009).doi:10.1038/nchembio.205
  • Wang, T., Duan, Y. Ligand entry and exit pathways in the beta2-adrenergic receptor. J. Mol. Biol. 392, 1102-1115 (2009).doi:10.1016/j.jmb.2009.07.093

Tutorial on application of RAMD

A tutorial describing the τRAMD process of setting up and running RAMD simulations for estimation of the relative residence time (τ) of a protein-small molecule complex can be found here.

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τRAMD

τ-random acceleration molecular dynamics (τRAMD) is a protocol based on the RAMD method for the ranking of drug candidates by their residence time and obtaining insights into ligand-target dissociation mechanism.

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AMBER patches

AMBER patches from the MCM group at HITS for RAMD and NPSA

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ADS

Analytically Defined molecular Surfaces (used within Molsurfer)

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ECM

ECM is now part of the SDA distribution

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Migrated to other research groups

LIGIN

Software for molecular docking using surface complementarity, see: Sobolev, V., Wade, R.C., Vriend, G. & Edelman, M. Molecular docking using surface complementarity, PROTEINS, 25, 120-129 (1996)

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metaPocket2

Webserver to identify pockets on protein surfaces to predict binding sites for ligands

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Methods and software available at other research groups

COMBINE analysis

Comparative Binding Energy Analysis LiteratureTutorialgCOMBINE

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UHBD

University of Houston Brownian Dynamics TutorialContact

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GRID

Computational method for identifying energetically favorable binding sites on biological molecules Tutorial

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Not updated software

ProSAT2

Select and group residue-based annotations and explore them interactively on a 3D structure of a protein

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ProSAT

Tool to map SwissProt features and Prosite patterns on to a 3D structure of a protein

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DSMM

Database of Simulated Molecular Motions

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TRAJAN

A Tool to Analyze Trajectories from Molecular Simulations

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pka calculation

Scripts for pKa calculations with UHBD

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