To understand atomic-level chemical and biophysical processes, molecular simulations are frequently used. Modeling of macromolecular interactions, protein folding, and drug creation are some examples of applications. Simulations typically use fast empirical potential functions, called empirical force fields (FFs). Rather than treating electron degrees of freedom explicitly, empirical force fields treat them implicitly by analyzing energy terms, parameters that are empirically tuned to replicate experimental and quantum chemistry reference data.
Alfa Chemistry offers its customers professional restrained electrostatic potential (RESP) calculations to meet their research needs. The RESP method is a highly respected and widely used simulation for assigning partial charges to molecules.RESP uses a quantum mechanical approach that produces chance overpolarization and therefore only roughly accounts for the self-polarization of molecules in the condensed phase.
RESP Charge Fitting Process
RESP charges are arguably the most suitable atomic charges for flexible small molecules used in molecular simulations (including kinetics, conformational analysis, molecular docking, etc) so far. The fitting of RESP charges is divided into the following two steps.
- Step 1: The charges are fitted using a hyperbolic penalty function that imposes weak restrictions (a=0.0005) on the non-hydrogen atoms, without constraining the atomic equivalence, and the charges of all atoms are fitted. This step allows the maximum degree of freedom for the atomic charge change to fully allow the polar atoms to fit the electrostatic potential as well as possible.
- Step 2: The charge is fitted using a hyperbolic penalty function that imposes a tighter constraint on the non-hydrogen atoms (a = 0.001), allowing only the charges of sp3 hybridized carbons, methylene carbons, and the hydrogens above them to be fitted, while the charges of the other atoms remain as they were at the end of the previous step. The fitting also constrains the charge of the hydrogen on each -CH3, =CH2, -CH2- group to maintain equivalence.
This procedure solves the problems associated with ordinary fitting of electrostatic potential charges for the simulation of flexible molecules without causing too much damage to the reproducibility of the electrostatic potential and the quality of the atomic charges from the imposed restrictions and limitations.
Alfa Chemistry uses the Multiwfn program for its calculation services, which includes the RESP calculation module for calculating fitted electrostatic potential charges. On the one hand it can be used to calculate RESP charges in standard form, and on the other hand it can calculate MK and CHELPG fitted electrostatic potential charges with custom charge constraints, atomic equivalence constraints, and penalty function parameters. Moreover the fitting process supports multiple conformations.
|Restrained Electrostatic Potential Calculation
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Using this module requires that the input file of Multiwfn contains wave function information. Due to the rich format supported by Multiwfn, almost all major quantization programs such as Gaussian, ORCA, GAMESS-US, NWChem, Molpro, etc. can be combined with Multiwfn to calculate RESP charges. The Gaussian we use is G16 A.03 and Multiwfn is version 3.6 (dev).
Fig 1. Training set of small molecules used for W-RESP parametrization. The data set was divided into three main subsets covering nucleic acids, amino acids, and other small organic compounds. (Janeček M, et al. 2021)
Our RESP Calculation services significantly reduce costs, facilitate further experimentation, and accelerate the drug design process for our global customers. Our personalized, full-service approach will meet your innovative learning needs. If you are interested in our services, please feel free to contact us. We would be happy to work with you and see you succeed!
- Janeček M, et al. (2021). "W-RESP: Well-Restrained Electrostatic Potential-Derived Charges. Revisiting the Charge Derivation Model." J. Chem. Theory Comput. 17(6): 3495-3509.