Ci. Bayly et al., A WELL-BEHAVED ELECTROSTATIC POTENTIAL BASED METHOD USING CHARGE RESTRAINTS FOR DERIVING ATOMIC CHARGES - THE RESP MODEL, Journal of physical chemistry, 97(40), 1993, pp. 10269-10280
We present a new approach to generating electrostatic potential (ESP)
derived charges for molecules. The major strength of electrostatic pot
ential derived charges is that they optimally reproduce the intermolec
ular interaction properties of molecules with a simple two-body additi
ve potential, provided, of course, that a suitably accurate level of q
uantum mechanical calculation is used to derive the ESP around the mol
ecule. Previously, the major weaknesses of these charges have been tha
t they were not easily transferable between common functional groups i
n related molecules, they have often been conformationally dependent,
and the large charges that frequently occur can be problematic for sim
ulating intramolecular interactions. Introducing restraints in the for
m of a penalty function into the fitting process considerably reduces
the above problems, with only a minor decrease in the quality of the f
it to the quantum mechanical ESP. Several other refinements in additio
n to the restrained electrostatic potential (RESP) fit yield a general
and algorithmic charge fitting procedure for generating atom-centered
point charges. This approach can thus be recommended for general use
in molecular mechanics, molecular dynamics, and free energy calculatio
ns for any organic or bioorganic system.