ARTICLE | doi:10.20944/preprints202208.0213.v1
Subject: Life Sciences, Biophysics Keywords: intermolecular binding affinity; drug target binding affinity; computer-aided drug design (CADD); artificial intelligence-integrated drug discovery (AIDD); machine learning
Online: 11 August 2022 (08:40:37 CEST)
Thanks to the continued development of experimental structural biology and the half-a-century old Protein Data Bank, 2021 saw a big step forward in the development of protein structure prediction with deep learning algorithms. Recently, DeepMinds AlphaFold has determined the structures of ∼ 200 million proteins from 1 million species. The speed of this progress raise the question of what becomes possible for computational drug discovery and design when we have a systems-wide account of the structures and motions of most proteins. Therefore, this article puts forward the concept of a general intermolecular binding affinity calculator (GIBAC): Kd = f(molA, molB, envPara), towards the acceleration of traditional computer-aided drug design (CADD) and artificial intelligence-integrated drug discovery (AIDD), for both small molecules and biologics such as therapeutic proteins.
ARTICLE | doi:10.20944/preprints202004.0522.v1
Subject: Chemistry, Physical Chemistry Keywords: RNA Nucleotides; Uracil; Intermolecular Binding; Cyclic Compounds
Online: 30 April 2020 (08:58:21 CEST)
Exogenous RNA comprises the genetic material associated with several diseases which require immediate treatment, and thus mechanisms to hinder intracellular translation and reproduction of RNA viral agents are of great importance. Applying recent developments from this lab in methods relating to the interaction of DNA with steroid hormones, cyclic compounds are presented for intermolecular binding to nucleic acids. The requirements to achieve binding with RNA nucleotide pairs are described, which involve at a minimum functional elements positioned to interact with the lateral phosphate groups for each of the RNA strands through coupling with a positively charged ion, such as Mg2+, Ca2+, or Zn2+ ions; and an intermolecular hydrogen bond with the oxygen element of uracil at the carbon two location. Additional features of the binding molecules are examined for enhancements and differentiation in binding capability and include aromatic groups that have both a structural role of steric hindrance and a functional role to stabilize the binding mechanisms. Several categories of cyclic compounds are associated to have specific binding capabilities, and the interaction of these structures with potential receptor molecules are evaluated for assessment in delivery and binding of the compound to nucleic acids.
ARTICLE | doi:10.20944/preprints202108.0500.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: molecular electric potentials; spatial confinement; intermolecular interactions
Online: 26 August 2021 (07:46:43 CEST)
In this theoretical study we report on molecular electrostatic potential (MEP) of titled molecules confined by repulsive potentials of cylindrical symmetry mimicking a topology. Our calculations show that the spatial restriction significantly changes the picture of MEP of molecules in quantitative and qualitative sense. In particular, the drastic changes of MEP as a function of the strength of spatial confinement are observed for the BrCN molecule. This preliminary study is the first step in the investigations of the behavior of MEP of molecular systems under the orbital compression.
ARTICLE | doi:10.20944/preprints202007.0671.v1
Subject: Engineering, General Engineering Keywords: Lignin; PAMAM dendrimer; electrospun fiber; intermolecular interactions
Online: 28 July 2020 (10:04:21 CEST)
Blending lignin as the second most abundant polymer in nature with nanostructured compounds such as dendritic polymers will not only add value to lignin, but also increase its application in various fields. In this study, softwood Kraft lignin/polyamidoamine dendritic polymer (PAMAM) blends were fabricated by solution electrospinning method to produce bead-free nanofiber mats. The mats were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), zeta potential, and thermogravimetry analysis (TGA). The chemical intermolecular interactions between lignin functional groups and abundant amino groups in PAMAM were investigated by FTIR and viscosity measurement. These interactions enhanced the mechanical and thermal characteristics of lignin/PAMAM mats, providing further potential applications at industry level.
ARTICLE | doi:10.20944/preprints201611.0008.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: nitrofurantoin; active pharmaceutical ingredient; 4-aminobenzoic acid; cocrystallization; intermolecular interaction; Raman spectroscopy; terahertz spectroscopy
Online: 1 November 2016 (09:54:24 CET)
Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.
Subject: Physical Sciences, Other Keywords: gravitational attraction; gravitational repulsion; antigravity; intermolecular forces; specific heat; thermal energy; adiabatic and isothermal expansion
Online: 29 January 2020 (10:35:17 CET)
The Author’s research series has revealed the existence in nature, of gravitational repulsion force, i,e., antigravity, which is proportional to the content of thermal energy of the particle. Such existence is in addition to the gravitational attraction force, accepted for several hundred years as proportional to mass. Notwithstanding such long acceptance, gravitational attraction acting on matter has totally been neglected in thermodynamic calculations in derivation of the ideal gas law. Both the antigravity force and the gravitational force have to be accommodated in an authentic elucidation of ideal gas behavior. Based on microscopic behavior of air molecules under varying temperature, this paper presents: firstly, the derivation of the mathematical model of gravitational repulsive force in matter; secondly, mathematical remodeling of the gravitational attractive force in matter.
ARTICLE | doi:10.20944/preprints201608.0198.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: huperzine A-AChE; molecular docking; intermolecular interaction; quantum chemical calculation; charge density distribution; atomic charges; dipole moment; electrostatic potential; toxicity analysis
Online: 23 August 2016 (12:33:27 CEST)
Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.