Assessing the Sequence Dependence of Pyrimidine-Pyrimidone (6-4) Photoproduct in a Duplex Double-Stranded DNA: A Challenge for Microsecond Range Simulation

Dynamics Simulations ◽

Close Sequence ◽

Sequence dependence of the (6-4)photoproduct dynamics when embedded in six 25-bp duplexes is evaluated along extensive unbiased and enhanced (replica exchange with solute tempering, REST2) molecular dynamics simulations. The structural reorganization as the central pyrimidines become covalently tethered is traced back in terms of non-covalent interactions, DNA bending and extrusion of adenines of the opposite strands. The close sequence pattern impacts the conformational landscape around the lesion, inducing a different upstream and downstream flexibilities. Moreover, REST2 simulations allow to probe structures possibly important for damaged DNA recognition. <br>

Catalytic Enantioselective Synthesis of Heterocyclic Vicinal Fluoroamines Using Asymmetric Protonation: A Method Development and Mechanistic Study

10.26434/chemrxiv.11920947 ◽

2020 ◽

Author(s):

Matthew Ashford ◽

Chao Xu ◽

john molloy ◽

Cameron Carpenter-Warren ◽

Alexandra Slawin ◽

...

Keyword(s):

Method Development ◽

Data Bank ◽

Enantioselective Synthesis ◽

Mechanistic Study ◽

Type Analysis ◽

Chiral Bronsted Acid ◽

Covalent Interactions ◽

Insight Into

<div> <div> <div> <p>A catalytic enantioselective synthesis of heterocyclic vicinal fluoroamines is reported. A chiral Brønsted acid promotes aza-Michael addition to fluoroalkenyl heterocycles to give a prochiral enamine intermediate, which undergoes asymmetric protonation upon rearomatization. The reaction accommodates a range of azaheterocycles and nucleophiles, generating the C–F stereocenter in high enantioselectivity, and is also amenable to stereogenic C–CF3 bonds. Extensive DFT calculations have provided insight into the reaction mechanism and the origin of catalyst selectivity. Crystal structure data shows the dominance of non-covalent interactions in the core structure conformation, enabling modulation of the conformational landscape. Ramachandran-type analysis of conformer distribution and protein data bank mining has indicated benzylic fluorination using this approach has potential for improved potency in several marketed drugs. </p> </div> </div> </div>

Non-Covalent Interactions Involving Aromatic Residues in Protein Structures: Stability and Dynamics in Membrane and Globular Proteins using Molecular Dynamics Simulations

Biophysical Journal ◽

10.1016/j.bpj.2009.12.3480 ◽

2010 ◽

Vol 98 (3) ◽

pp. 635a-636a

Author(s):

Alok Jain ◽

Ramasubbu Sankararamakrishnan

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Protein Structures ◽

Globular Proteins ◽

Aromatic Residues ◽

Dynamics Simulations ◽

Floppy SOX: Mutual Induced Fit in HMG (High-Mobility Group) Box-DNA Recognition

Molecular Endocrinology ◽

10.1210/mend.15.3.0617 ◽

2001 ◽

Vol 15 (3) ◽

pp. 353-362 ◽

Cited By ~ 38

Author(s):

Michael A. Weiss

Keyword(s):

Tertiary Structure ◽

Dna Bending ◽

Dna Recognition ◽

High Mobility ◽

High Mobility Group ◽

Base Pairs ◽

Induced Fit ◽

Sequence Dependence ◽

Hmg Box ◽

Dna Minor Groove

Abstract The high-mobility group (HMG) box defines a DNA-bending motif of broad interest in relation to human development and disease. Major and minor wings of an L-shaped structure provide a template for DNA bending. As in the TATA-binding protein and a diverse family of factors, insertion of one or more side chains between base pairs induces a DNA kink. The HMG box binds in the DNA minor groove and may be specific for DNA sequence or distorted DNA architecture. Whereas the angular structures of non-sequence-specific domains are well ordered, free SRY and related autosomal SOX domains are in part disordered. Observations suggesting that the minor wing lacks a fixed tertiary structure motivate the hypothesis that DNA bending and stabilization of protein structure define a coupled process. We further propose that mutual induced fit in SOX-DNA recognition underlies the sequence dependence of DNA bending and enables the induction of promoter-specific architectures.

Dynamic chiral self-recognition in aromatic dimers of styrene oxide revealed by rotational spectroscopy

Communications Chemistry ◽

10.1038/s42004-021-00468-4 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Sérgio R. Domingos ◽

Cristóbal Pérez ◽

Nora M. Kreienborg ◽

Christian Merten ◽

Melanie Schnell

Keyword(s):

Styrene Oxide ◽

Intermolecular Forces ◽

Molecular Structures ◽

Conformational Space ◽

Rotational Spectroscopy ◽

Self Recognition ◽

Quantum Chemistry Calculations ◽

AbstractChiral molecular recognition is a pivotal phenomenon in biomolecular science, governed by subtle balances of intermolecular forces that are difficult to quantify. Non-covalent interactions involving aromatic moieties are particularly important in this realm, as recurring motifs in biomolecular aggregation. In this work, we use high-resolution broadband rotational spectroscopy to probe the dynamic conformational landscape enclosing the self-pairing topologies of styrene oxide, a chiral aromatic system. We reach a definite assignment of four homochiral and two heterochiral dimers using auxiliary quantum chemistry calculations as well as structure-solving methods based on experimental isotopic information. A complete picture of the dimer conformational space is obtained, and plausible routes for conformational relaxation are derived. Molecular structures are discussed in terms of conformational flexibility, the concerted effort of weak intermolecular interactions, and their role in the expression of the molecular fit.

Exploring the non-covalent interactions behind the formation of amine–water complexes: The case of the N-allylmethylamine monohydrate

Physical Chemistry Chemical Physics ◽

10.1039/d1cp00420d ◽

2021 ◽

Author(s):

Weslley Guilherme Dias de Paiva Silva ◽

Tamanna Poonia ◽

Jennifer van Wijngaarden

Keyword(s):

Quantum Chemistry ◽

Rotational Spectroscopy ◽

Quantum Chemistry Calculations ◽

First Time ◽

The conformational landscape of the monohydrated complex of N-allylmethylamine (AMA–w) was investigated for the first time using rotational spectroscopy from 8–20 GHz and quantum chemistry calculations. From a total of...

Conformational landscape of isolated capped amino acids: on the nature of non-covalent interactions

The European Physical Journal D ◽

10.1140/epjd/e2017-80187-5 ◽

2017 ◽

Vol 71 (8) ◽

Cited By ~ 2

Author(s):

Jorge González ◽

Rodrigo Martínez ◽

José A. Fernández ◽

Judith Millan

Keyword(s):

Amino Acids ◽

Catalytic Enantioselective Synthesis of Heterocyclic Vicinal Fluoroamines Using Asymmetric Protonation: A Method Development and Mechanistic Study

10.26434/chemrxiv.11920947.v1 ◽

2020 ◽

Author(s):

Matthew Ashford ◽

Chao Xu ◽

john molloy ◽

Cameron Carpenter-Warren ◽

Alexandra Slawin ◽

...

Keyword(s):

Method Development ◽

Data Bank ◽

Enantioselective Synthesis ◽

Mechanistic Study ◽

Type Analysis ◽

Chiral Bronsted Acid ◽

Covalent Interactions ◽

Insight Into

<div> <div> <div> <p>A catalytic enantioselective synthesis of heterocyclic vicinal fluoroamines is reported. A chiral Brønsted acid promotes aza-Michael addition to fluoroalkenyl heterocycles to give a prochiral enamine intermediate, which undergoes asymmetric protonation upon rearomatization. The reaction accommodates a range of azaheterocycles and nucleophiles, generating the C–F stereocenter in high enantioselectivity, and is also amenable to stereogenic C–CF3 bonds. Extensive DFT calculations have provided insight into the reaction mechanism and the origin of catalyst selectivity. Crystal structure data shows the dominance of non-covalent interactions in the core structure conformation, enabling modulation of the conformational landscape. Ramachandran-type analysis of conformer distribution and protein data bank mining has indicated benzylic fluorination using this approach has potential for improved potency in several marketed drugs. </p> </div> </div> </div>