Design Two Novel Tetrahydroquinoline Derivatives against Anticancer Target LSD1 with 3D-QSAR Model and Molecular Simulation.

Lysine-specific demethylase 1 (LSD1) is a histone-modifying enzyme, which is a significant target for anticancer drug research. In this work, 40 reported tetrahydroquinoline-derivative inhibitors targeting LSD1 were studied to establish the three-dimensional quantitative structure-activity relationship (3D-QSAR). The established models CoMFA (Comparative Molecular Field Analysis (q = 0.

Toxic Effect of Fullerene and Its Derivatives upon the Transmembrane β-Adrenergic Receptors.

Numerous experiments have revealed that fullerene (C) and its derivatives can bind to proteins and affect their biological functions. In this study, we explored the interaction between fullerine and the β-adrenergic receptor (βAR). The MD simulation results show that fullerene binds with the extracellular loop 2 (ECL2) and intracellular loop 2 (ICL2) of βAR through hydrophobic interactions and π-π stacking interactions.

Ultra-coarse-graining modeling of liquid water.

It is a great challenge to develop ultra-coarse-grained models in simulations of biological macromolecules. In this study, the original coarse-graining strategy proposed in our previous work [M. Li and J.

A three-point coarse-grained model of five-water cluster with permanent dipoles and quadrupoles.

As coarse-grained (CG) studies of large biomolecules increase, developments of reliable CG solvent models become particularly important. In this work, we reduce five water molecules into a three-point CG model with permanent dipole and quadrupole moments. In the CG force field, the modified Morse potential is utilized and an ideal three-water cluster is designed to derive CG-level permanent multipoles.

Double-Well Ultra-Coarse-Grained Model to Describe Protein Conformational Transitions.

The double-well model is usually used to describe the conformational transition between two states of a protein. Since conformational changes usually occur within a relatively large time scale, coarse-grained models are often used to accelerate the dynamic process due to their inexpensive computational cost. In this work, we develop a double-well ultra-coarse-grained (DW-UCG) model to describe the conformational transitions of the adenylate kinase, glutamine-binding protein, and lactoferrin.

How CuCl and CuCl Insert into C-N Bonds of Diazo Compounds: An Electronic Structure and Mechanistic Study.

The transition-metal Cu catalysts CuCl and CuCl have been widely employed to catalyze a series of chemical reactions with diazo compounds because of their high efficiency and selectivity. However, how to yield the active Cu carbene species from the Cu catalysts and diazo compounds still remains unclear. In this work, we performed a comprehensive theoretical investigation on the electronic structures of CuCl and CuCl in solution.

Atomic-level reconstruction of biomolecules by a rigid-fragment- and local-frame-based (RF-LF) strategy.

Coarse-grained (CG) model has been a powerful tool in bridging the gap between theoretical studies and experimental phenomena in biological computing field. The reconstruction from a CG model to an atomic-detail structure is especially important in CG studies of biological systems. In this work, a rigid-fragment- and local-frame-based (RF-LF) backmapping method was proposed to achieve reverse mapping from CG models to atomic-level structures.

Determining Optimal Coarse-Grained Representation for Biomolecules Using Internal Cluster Validation Indexes.

The development of ultracoarse-grained models for large biomolecules needs to derive the optimal number of coarse-grained (CG) sites to represent the targets. In this work, we propose to use the statistical internal cluster validation indexes to determine the optimal number of CG sites that are optimized based on the essential dynamics coarse-graining method. The calculated curves of Calinski-Harabasz and Silhouette Coefficient indexes exhibit the extrema corresponding to the similar CG numbers.

Origins of Protons in C-H Bond Insertion Products of Phenols: Proton-Self-Sufficient Function via Water Molecules.

Water molecules can serve as proton shuttles for proton transfer in the C-H bond insertion reactions catalyzed by transition metal complexes. Recently, the control experiments performed for C-H bond insertion of phenol and anisol by gold carbenes show that large discrepancy exists in the yields of hydrogenated and deuterated products. Thus, we conducted a detailed theoretical analysis on the function of water molecules in the C-H bond insertion reactions.

Performance Comparison of Systematic Methods for Rigorous Definition of Coarse-Grained Sites of Large Biomolecules.

Construction of coarse-grained (CG) models for large biomolecules used for multiscale simulations demands a rigorous definition of CG sites for them. Several coarse-graining methods such as the simulated annealing and steepest descent (SASD) based on the essential dynamics coarse-graining (ED-CG) or the stepwise local iterative optimization (SLIO) based on the fluctuation maximization coarse-graining (FM-CG), were developed to do it. However, the practical applications of these methods such as SASD based on ED-CG are subject to limitations because they are too expensive.

DFT Calculations on the Mechanism of Transition-Metal-Catalyzed Reaction of Diazo Compounds with Phenols: O-H Insertion versus C-H Insertion.

The reaction of diazo compounds with transition-metal carbenes is an efficient way to achieve the functionalization of chemical bonds in organic molecules, especially for the C-H and O-H bonds. However, the selective mechanisms of C-H and O-H bond insertions by various metal carbenes such as Rh and Cu complexes are not quite clear. In this work, we performed a comprehensively theoretical investigation of the phenol C-H and O-H bonds inserted by Rh and Cu carbenes by using DFT calculations.

Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization.

Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules.

Mechanistic Investigation of Aromatic C(sp(2))-H and Alkyl C(sp(3))-H Bond Insertion by Gold Carbenes.

It was recently reported that the gold-carbenes have an unprecedented catalysis toward the functionalization of C(sp(2))-H bonds of aromatic compounds. However, the associated mechanisms of C(sp(2))-H bonds inserted by gold-carbenes have not been comprehensively understood. We carried out a detailed mechanistic investigation of gold-carbene insertion into the C(sp(2))-H bond of anisole by means of theoretical calculations and control experiments.

Origins of unique gold-catalysed chemo- and site-selective C-H functionalization of phenols with diazo compounds.

In past decade, gold revealed more and more unique properties in carbene chemistry. It was disclosed in our recent communication ( 2014, , 6904) that gold carbenes have unprecedented chemo- and site-selectivity and ligand effect toward the functionalization of C-H bonds in phenols. In this full article, we report a comprehensively combined theoretical and experimental study on the mechanism of the insertion of gold carbenes into C-H and O-H bonds in phenol.