A method of using a computer processor to analyze electrical signals and data representative of a first molecule to determine conformational free energy of the first molecule so as to determine whether the first molecule is more stable than a second molecule, wherein both molecules have a predefined connectivity and exist in a predefined environment, comprising: (a) generating a set of data representative of low-energy minimum conformations of the first molecule derived from connectivity of the first molecule, a potential energy function, and a conformational search method; (b) determining conformational free energy of the first molecule by calculating a configuration integral in all degrees of freedom based upon a contribution of each conformation of the set of conformations of the first molecule, wherein the configuration integral is calculated by: (i) performing importance sampling multidimensional Monte Carlo integration over a multidimensional volume enclosing a current conformation of the first molecule in a conformational space, wherein the volume is dependent on harmonic vibrational frequencies of the current conformation and temperature, wherein the importance sampling comprises preferentially sampling regions of the volume in conformational space associated with the current conformation which regions have dominant contribution to the conformational free energy of the current conformation, and wherein the importance sampling utilizes a physical background consisting essentially of normal modes of vibration of the first molecule and the sampling is performed using an atomic coordinate transformation which is based on eigenvectors of a Hessian matrix associated with the current conformation; (ii) repeating step (i) for each conformation in the set of data; and (iii) summing the conformational contributions determined in steps (i-ii) so as to determine a total configuration integral for the first molecule to determine the conformational free energy of the first molecule; (c) repeating steps (a)-(b) for the second molecule; and (d) comparing the conformational free energy of the first molecule with the conformational free energy of the second molecule and determining which molecule has lower conformational free energy to determine which molecule is more stable.

1. A computer-based method of designing chemical structures having a preselected functional characteristic, comprising the steps of: (a) producing a physical model of a simulated receptor phenotype encoded in a linear character sequence, and providing a set of target molecules sharing at least one quantifiable functional characteristic; (b) for each target molecule; (i) calculating an affinity between the receptor and the target molecule in each of a plurality of orientations using an effective affinity calculation; (ii) calculating a sum affinity by summing the calculated affinities; (iii) identifying a maximal affinity; (c) using the calculated sum and maximal affinities to: (i) calculate a maximal affinity correlation coefficient between the maximal affinities and the quantifiable functional characteristic; (ii) calculate a sum affinity correlation coefficient between the sum affinities and the quantifiable functional characteristic; (d) using the maximal correlation coefficient and sum correlation coefficient to calculate a fitness coefficient; (e) altering the structure of the receptor and repeating steps (b) through (d) until a population of receptors having a preselected fitness coefficient are obtained; (f) providing a physical model of a chemical structure encoded in a molecular linear character sequence, calculating an affinity between the chemical structure and each receptor in a plurality of orientations using said effective affinity calculation, using the calculated affinities to calculate an affinity fitness score; (g) altering the chemical structure to produce a variant of the chemical structure and repeating step (f); and (h) retaining and further altering those variants of the chemical structure whose affinity score approaches a preselected affinity score.

1. A system for generating compounds having a prescribed set of activity/properties, comprising: chemical synthesis means for synthesizing, in accordance with synthesis instructions, a directed diversity chemical library comprising a plurality of chemical compounds; analysis means for analyzing said chemical compounds to obtain structure-activity data pertaining thereto; comparing means for comparing said structure-activity data of said chemical compounds against said prescribed set of activity/properties to identify any of said chemical compounds substantially conforming to said prescribed set of activity/properties; classifying means for classifying said identified chemical compounds as lead compounds; structure-activity model derivation means for analyzing said structure-activity data of said compounds and historical structure-activity data pertaining to compounds synthesized and analyzed in the past to derive structure-activity models having enhanced predictive and discriminating capabilities; reagent identifying means for identifying, in accordance with said structure-activity models, reagents from a reagent database that, when combined, will produce a set of compounds predicted to exhibit activity/properties more closely matching said prescribed set of activity/properties; and synthesis instruction generating means for generating synthesis instructions that, when executed, enable said chemical synthesis means to synthesize said set of compounds.