  Evaluating accessible conformational space is computationally expensive and
thermal motions are partly neglected in computer models of molecular
interactions. This produces error into the estimates of binding strength. We
introduce a method for modelling interactions so that structural flexibility is
inherently taken into account. It has a statistical model for 3D properties of
'nonlocal' contacts and a physics based description of 'local' interactions,
based on mechanical torque. The form of the torque barrier is derived using a
representation of the local electronic structure, which is presumed to improve
transferability, compared to traditional force fields. The nonlocal contacts
are more distant than 1-4 interactions and Target-atoms are represented by 3D
probability densities. Probability mass quantifies strength of contact and is
calculated as an overlap integral. Repulsion is described by negative
probability density, allowing probability mass to be used as the descriptor of
contact preference. As a result, we are able to transform the high-dimensional
problem into a simpler evaluation of three-dimensional integrals. We outline
how this scoring function gives a tool to study the enthalpy--entropy
compensation and demonstrate the feasibility of our approach by evaluating
numerical probability masses for chosen side chain to main chain contacts in a
lysine dipeptide structure.
