Computational Drug Discovery and Design
alchemical path in Gromacs. The same procedure is carried out for the ligand in solution. In this case, however, the restraints ...
previous paragraphs; here we report them more explicitly and with a brief explanation: l Use a soft-core potential for decouplin ...
core potential for the electrostatic interactions as well (see Note 3)[60, 61]. l Avoid changing the net charge of the system ac ...
orientation is kinetically trapped in a different conformation as compared to the target one, large and unconverged free energy ...
states [76, 77](seeNote 8). The HREX approach has low compu- tational overhead and can result in enhanced sampling, improved pha ...
being collected. Nonetheless, it is important to try to exclude nonequilibrated regions of the simulations from the analysis and ...
Fig. 5Overlap matrices for the decoupling of a ligand from solution. The overlap matrix at the top was obtained for the decoupli ...
spacing. In general, a good phase space overlap is attainable for the decoupling of the ligand from solution, but can be more ch ...
In this section, we provided a brief overview of how to analyze alchemical free energy results while also mentioning some recom- ...
Considerations about the quality of the starting structure and the modeling of the system’s chemistry are important too. For ins ...
couple-lambda0andcouple-lambda1define the state of the intermolecular interactions atλvalues of zero and one, respectively; in t ...
together with the ligand, so that the change in net charge would be compensated. This is however likely to introduce spurious fr ...
interpolate between the force constant (and equilibrium posi- tions) in stateAandB. [ intermolecular_interactions] [ bonds ] ; a ...
into account [33]. A symmetry correction applies when: (a) the ligand is symmetric or contains a symmetric moiety; (b) the equiv ...
the MRC, BBSRC, and the John Fell Fund. We thank the Advanced Research Computing (ARC) facility, the EPSRC UK National Ser- vice ...
nonequilibrium measurements using maximum-likelihood methods. Phys Rev Lett 91(14):140601 Shirts MR, Chodera JD (2008) Statisti ...
χ(2) dihedral angles. J Chem Theory Comput 8(9):3257–3273 Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development ...
fields for proteins. J Chem Phys 119 (11):5740–5761 Kelly E, Seth M, Ziegler T (2004) Calculation of free energy profiles for e ...
Shirts MR, Pande VS (2005) Solvation free energies of amino acid side chain analogs for common molecular mechanics water models ...
Chapter 12 Evaluation of Protein–Ligand Docking by Cyscore Yang Cao, Wentao Dai, and Zhichao Miao Abstract Protein–ligand dockin ...
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