Phase Shift Analysis for Alpha-alpha Elastic Scattering using Phase Function Method for Gaussian Local Potential

The phase shifts for α- α scattering have been modeled using a two parameter Gaussian local potential. The time independent Schrodinger equation (TISE) has been solved iteratively using Monte-Carlo approach till the S and D bound states of the numerical solution match with the experimental binding energy data in a variational sense. The obtained potential with best fit parameters is taken as input for determining the phase-shifts for the S channel using the non-linear first order differential equation of the phase function method (PFM). It is numerically solved using 5th order Runge-Kutta (RK-5) technique. To determine the phase shifts for the ℓ=2 and 4 scattering state i.e. D and G-channel, the inversion potential parameters have been determined using variational Monte-Carlo (VMC) approach to minimize the realtive mean square error w.r.t. the experimental data.

The Inter-Nucleon Up-to-Down Quark Bond and its Implications for Nuclear Binding

This paper describes an interesting and potentially significant phenomenon regarding the properties of up and down quarks within the nucleus, specifically how the possible internucleon bonding of these quarks may affect the bonding energy of the nuclear force. A very simple calculation is used, which involves a bond between two internucleon up and down quarks. This simple calculation does not specify the shape or structure for the nucleus, rather this calculation only examines the energy of all possible internucleon up-to-down bonds that may be formed within a quantum nucleus. A comparison of this calculated binding energy is made to the experimental binding energy with remarkably good results. The potential significance and implications of this noteworthy finding are discussed.

A single molecular distance predicts agonist binding energy in nicotinic receptors

Agonists turn on receptors because they bind more strongly to active (R*) versus resting (R) conformations of their target sites. Here, to explore how agonists activate neuromuscular acetylcholine receptors, we built homology models of R and R* neurotransmitter binding sites, docked ligands to those sites, ran molecular dynamics simulations to relax (“equilibrate”) the structures, measured binding site structural parameters, and correlated them with experimental agonist binding energies. Each binding pocket is a pyramid formed by five aromatic amino acids and covered partially by loop C. We found that in R* versus R, loop C is displaced outward, the pocket is smaller and skewed, the agonist orientation is reversed, and a key nitrogen atom in the agonist is closer to the pocket center (distance dx) and a tryptophan pair but farther from αY190. Of these differences, the change in dx shows the largest correlation with experimental binding energy and provides a good estimate of agonist affinity, efficacy, and efficiency. Indeed, concentration–response curves can be calculated from just dx values. The contraction and twist of the binding pocket upon activation resemble gating rearrangements of the extracellular domain of related receptors at a smaller scale.

An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings

The Nwat-MMGBSA method, whose theory has been described in Maffucci & Contini, JCTC 2013, 9, 2706, is based on the inclusion as part of the receptor of a given number of water molecules (Nwat) which are the closest to a residue (generally the ligand) or to a selection of residues (the contact interface) in each frame of the MD simulation. The method was shown to improve the correlation between predicted and experimental binding energy in both ligand-receptor and protein-protein complexes (Maffucci & Contini, JCIM 2016, 56, 1692). Here, we report on the optimization of the Nwat-MMGBSA protocol for its use to rescore docking results. We also report an automatic workflow, based on three independent scripts (which can be concatenated in a fully automated procedure) to easily employ Nwat-MMGBSA rescoring in virtual screening application. The protocol has been tuned using three different examples, and then tested in two retrospective virtual screening examples. In each example, the Nwat-MMGBSA method has been compared with the standard MMGBSA approach (Nwat=0). A link to download the scripts, working examples and tutorials is also provided.<br><br>

An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings

The Nwat-MMGBSA method, whose theory has been described in Maffucci & Contini, JCTC 2013, 9, 2706, is based on the inclusion as part of the receptor of a given number of water molecules (Nwat) which are the closest to a residue (generally the ligand) or to a selection of residues (the contact interface) in each frame of the MD simulation. The method was shown to improve the correlation between predicted and experimental binding energy in both ligand-receptor and protein-protein complexes (Maffucci & Contini, JCIM 2016, 56, 1692). Here, we report on the optimization of the Nwat-MMGBSA protocol for its use to rescore docking results. We also report an automatic workflow, based on three independent scripts (which can be concatenated in a fully automated procedure) to easily employ Nwat-MMGBSA rescoring in virtual screening application. The protocol has been tuned using three different examples, and then tested in two retrospective virtual screening examples. In each example, the Nwat-MMGBSA method has been compared with the standard MMGBSA approach (Nwat=0). A link to download the scripts, working examples and tutorials is also provided.<br><br>

Binding Energy of with Two-Channel Separable Potentials

Using the two-channel separable potentials of Nogami and Satoh, which are fitted to the hyperon-nucleon scattering data, the Λ binding energy in [Formula: see text] has been calculated using the model of Law and Nguyen. We find that the binding energy is sensitive to the coupling to the Σ channel. The results indicate that it is possible to obtain agreement with the experimental binding energy of [Formula: see text].