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

The determinants of successful partnering: a transaction cost perspective

Support is emerging for the assertion that partnering can have a significant beneficial influence on project relationships and project outcomes. However, not all of the evidence bears this out: there are some examples of less-than-successful experiments with partnering approaches. Questions quite naturally arise as to whether any particular elements or aspects of partnering have differed in some of the documented examples, thus giving rise to their relative success or failure. In order to answer such questions there is a need for a theoretical framework against which to analyse the relative performance of partnering projects. In this paper, the authors propose an approach based upon aspects of Transaction Cost Economics (TCE) theory. It is argued that two main factors, contractual incompletedness and opportunism, are fundamental in determining whether project relationships are adversarial or not. The validity of the approach is examined by applying it retrospectively to a strategic partnering agreement involving more than 80 individual building projects. This agreement had been the subject of a four-year study and had been found to produce benefits in a number of areas, not least in the avoidance of conflict and disputes. After analysis, evidence for the reduction of contractual incompletedness was mixed, however the opportunistic inclinations of the participants (specifically, the contractors) were effectively attenuated by a clearly observable combination of factors, which included preselection criteria, and the use of appropriate management and commercial frameworks in which to operate. The case study suggests a prima facie validity to the analytical approach that was adopted, which merits further testing: the next stages being to develop and refine the framework, and to carry out comparative multi-case research on a number of different partnering projects