Implicit Ligand Theory: Rigorous Binding Free Energies and Thermodynamic Expectations from Molecular Docking

A rigorous formalism for estimating noncovalent binding free energies and thermodynamic expectations from calculations in which receptor configurations are sampled independently from the ligand is derived. Due to this separation, receptor configurations only need to be sampled once, facilitating the use of binding free energy calculations in virtual screening. Demonstrative calculations on a host-guest system yield good agreement with previous free energy calculations and isothermal titration calorimetry measurements. Implicit ligand theory provides guidance on how to improve existing molecular docking algorithms and insight into the concepts of induced fit and conformational selection in noncovalent macromolecular recognition.Comment: 21 pages, 2 figures, 4 tables, 3 supplemental figures, 2 supplemental table

Optimized replica gas estimation of absolute integrals and partition functions

In contrast with most Monte Carlo integration algorithms, which are used to estimate ratios, the replica gas identities recently introduced by Adib enable the estimation of absolute integrals and partition functions using multiple copies of a system and normalized transition functions. Here, an optimized form is presented. After generalizing a replica gas identity with an arbitrary weighting function, we obtain a functional form that has the minimal asymptotic variance for samples from two replicas and is provably good for a larger number. This equation is demonstrated to improve the convergence of partition function estimates in a 2D Ising model.Comment: 8 pages, 2 figure

First record of the sawfly family Xyelidae (Hymenoptera) from Malta

Xyela cf. altenhoferi Blank, 2013 is recorded from Buskett (Malta). Its host is Pinus halepensis. This is the first species of the sawfly family Xyelidae to be found in the Maltese Islands.peer-reviewe