Determination of side-chain-rotamer and side-chain and backbone virtual-bond-stretching potentials of mean force from AM1 energy surfaces of terminally-blocked amino-acid residues, for coarse-grained simulations of protein structure and folding. I. The method

I have been given the last word in this discussion, and I take advantage of the opportunity with some diffidence. The discussion has ranged widely over the field, but the major issues under dispute have been in the province of the crystallographers. I certainly cannot count myself among them, and am often quite incompetent to judge of the validity of what they say. However, the issues involved are of such importance to protein chemists, and to many biologists as well, that I offer comments on some of them. First of all, it is really amazing, to one who has been in the field of protein chemistry for a quarter of a century, that this discussion could be carried on, at this level, in the year 1952. Even five years ago it would have seemed almost incredible that we could have begun so soon to probe so deeply into the finer details of protein structure. The possibility of thinking in these terms has certainly been profoundly influenced by a development which has not found any but an incidental place in to-day’s discussion—the determination of the sequence of amino-acid residues in polypeptide chains (Sanger 1952). The outstanding achievement in this field hitherto is of course the complete determination of the sequence in the two kinds of peptide chain in insulin, by Sanger & Tuppy (1951) and Sanger & Thompson (1952). It appears that it remains only to fix the nature of the disulphide cross-links in order to have a complete structural formula for at least one protein.

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Determination of Effective Potentials for the Stretching of Cα···Cα Virtual Bonds in Polypeptide Chains for Coarse-Grained Simulations of Proteins from ab Initio Energy Surfaces of N-Methylacetamide and N-Acetylpyrrolidine

Journal of Chemical Theory and Computation ◽

10.1021/ct2008439 ◽

2012 ◽

Vol 8 (4) ◽

pp. 1334-1343 ◽

Cited By ~ 26

Author(s):

Adam K. Sieradzan ◽

Harold A. Scheraga ◽

Adam Liwo

Keyword(s):

Ab Initio ◽

Coarse Grained ◽

Effective Potentials ◽

Coarse Grained Simulations ◽

Energy Surfaces ◽

Polypeptide Chains

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Polypeptides Folding: Rules for the Calculation of the Backbone Dihedral Angles φ starting from the Amino Acid Sequence

10.26434/chemrxiv.12000132 ◽

2020 ◽

Author(s):

Michele Larocca

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Theoretical Approach ◽

Polypeptide Chain ◽

Hydrophobic Effect ◽

Side Chain ◽

Dihedral Angles ◽

Mechanical Forces ◽

Specific Chemical

<p>Protein folding is strictly related to the determination of the backbone dihedral angles and depends on the information contained in the amino acid sequence as well as on the hydrophobic effect. To date, the type of information embedded in the amino acid sequence has not yet been revealed. The present study deals with these problematics and aims to furnish a possible explanation of the information contained in the amino acid sequence, showing and reporting rules to calculate the backbone dihedral angles φ. The study is based on the development of mechanical forces once specific chemical interactions are established among the side chain of the residues in a polypeptide chain. It aims to furnish a theoretical approach to predict backbone dihedral angles which, in the future, may be applied to computational developments focused on the prediction of polypeptide structures.</p>

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Schistosomal Sulfotransferase Interaction with Oxamniquine Involves Hybrid Mechanism of Induced-fit and Conformational Selection

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190708103132 ◽

2020 ◽

Vol 16 (4) ◽

pp. 451-459 ◽

Cited By ~ 1

Author(s):

Fortunatus C. Ezebuo ◽

Ikemefuna C. Uzochukwu

Keyword(s):

Molecular Dynamics ◽

Amino Acid ◽

Binding Energy ◽

Binding Site ◽

Conformational Dynamics ◽

Side Chain ◽

Amino Acid Residues ◽

Conformational Selection ◽

Hybrid Mechanism ◽

Dynamics Simulations

Background: Sulfotransferase family comprises key enzymes involved in drug metabolism. Oxamniquine is a pro-drug converted into its active form by schistosomal sulfotransferase. The conformational dynamics of side-chain amino acid residues at the binding site of schistosomal sulfotransferase towards activation of oxamniquine has not received attention. Objective: The study investigated the conformational dynamics of binding site residues in free and oxamniquine bound schistosomal sulfotransferase systems and their contribution to the mechanism of oxamniquine activation by schistosomal sulfotransferase using molecular dynamics simulations and binding energy calculations. Methods: Schistosomal sulfotransferase was obtained from Protein Data Bank and both the free and oxamniquine bound forms were subjected to molecular dynamics simulations using GROMACS-4.5.5 after modeling it’s missing amino acid residues with SWISS-MODEL. Amino acid residues at its binding site for oxamniquine was determined and used for Principal Component Analysis and calculations of side-chain dihedrals. In addition, binding energy of the oxamniquine bound system was calculated using g_MMPBSA. Results: The results showed that binding site amino acid residues in free and oxamniquine bound sulfotransferase sampled different conformational space involving several rotameric states. Importantly, Phe45, Ile145 and Leu241 generated newly induced conformations, whereas Phe41 exhibited shift in equilibrium of its conformational distribution. In addition, the result showed binding energy of -130.091 ± 8.800 KJ/mol and Phe45 contributed -9.8576 KJ/mol. Conclusion: The results showed that schistosomal sulfotransferase binds oxamniquine by relying on hybrid mechanism of induced fit and conformational selection models. The findings offer new insight into sulfotransferase engineering and design of new drugs that target sulfotransferase.

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Synthesis and conformation of sequential basic polypeptides with branched and linear side chains

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19852925 ◽

1985 ◽

Vol 50 (12) ◽

pp. 2925-2936 ◽

Cited By ~ 2

Author(s):

Štěpánka Štokrová ◽

Jan Pospíšek ◽

Jaroslav Šponar ◽

Karel Bláha

Keyword(s):

Amino Acid ◽

Salt Concentration ◽

Salt Solution ◽

Theoretical Work ◽

Side Chain ◽

Amino Acid Residues ◽

Cd Spectra ◽

Low Salt ◽

Conformational Freedom ◽

Basic Polypeptides

Polypeptides (Lys-X-Ala)n and (Lys-X-Gly)n in which X represents residues of isoleucine and norleucine, respectively, and polypeptide (Tle-Lys-Ala)n, were synthesized via polymerization of 1-hydroxysuccinimidyl esters of the appropriate tripeptides to complete previously studied series. Circular dichroism (CD) spectra of the respective polymers were measured as a function of pH and salt concentration of the medium. The results were correlated with those obtained previously with the same series containing different amino acid residues at the X-position. The helix forming ability of the polypeptides (Lys-X-Ala)n with linear X side chain was found to be independent of the length. In the series (Lys-X-Gly)n the unordered conformation was the most probable one except (Lys-Ile-Gly)n. This polymer assumed the β conformation even in low salt solution at neutral pH. An agreement with some theoretical work concerned with the restriction of conformational freedom of amino acid residue branching at Cβ atom with our experimental results is evident.

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Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19911963 ◽

1991 ◽

Vol 56 (9) ◽

pp. 1963-1970 ◽

Cited By ~ 3

Author(s):

Jan Hlaváček ◽

Václav Čeřovský ◽

Jana Pírková ◽

Pavel Majer ◽

Lenka Maletínská ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Point Of View ◽

Biologically Active ◽

Side Chain ◽

Amino Acid Residues ◽

Cholecystokinin Octapeptide ◽

Biological Tests ◽

Biological Potency ◽

Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

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Effect of roasting temperature on lipid and protein oxidation and amino acid residue side chain modification of beef patties

RSC Advances ◽

10.1039/d1ra03151a ◽

2021 ◽

Vol 11 (35) ◽

pp. 21629-21641

Author(s):

Chao Xia ◽

Pingping Wen ◽

Yaming Yuan ◽

Xiaofan Yu ◽

Yijing Chen ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Residue ◽

Protein Oxidation ◽

Relative Number ◽

Side Chain ◽

Amino Acid Residues ◽

Beef Patties ◽

Lipid And Protein Oxidation ◽

Roasting Temperature

The relative number of peptides modified by the amino acid residues of actin from raw beef patties and those cooked at different roasting temperatures.

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Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence

Molecules ◽

10.3390/molecules26020444 ◽

2021 ◽

Vol 26 (2) ◽

pp. 444

Author(s):

Motoharu Hirano ◽

Chihiro Saito ◽

Hidetomo Yokoo ◽

Chihiro Goto ◽

Ryuji Kawano ◽

...

Keyword(s):

Antimicrobial Activity ◽

Amino Acid ◽

Hemolytic Activity ◽

Helical Structure ◽

Antimicrobial Activities ◽

Side Chain ◽

Membrane Disruption ◽

Amino Acid Residues ◽

Electrophysiological Measurements ◽

Cell Membrane Disruption

Magainin 2 (Mag2), which was isolated from the skin of the African clawed frog, is a representative antimicrobial peptide (AMP) that exerts antimicrobial activity via microbial membrane disruption. It has been reported that the helicity and amphipathicity of Mag2 play important roles in its antimicrobial activity. We investigated and recently reported that 17 amino acid residues of Mag2 are required for its antimicrobial activity, and accordingly developed antimicrobial foldamers containing α,α-disubstituted amino acid residues. In this study, we further designed and synthesized a set of Mag2 derivatives bearing the hydrocarbon stapling side chain for helix stabilization. The preferred secondary structures, antimicrobial activities, and cell-membrane disruption activities of the synthesized peptides were evaluated. Our analyses revealed that hydrocarbon stapling strongly stabilized the helical structure of the peptides and enhanced their antimicrobial activity. Moreover, peptide 2 stapling between the first and fifth position from the N-terminus showed higher antimicrobial activity than that of Mag2 against both gram-positive and gram-negative bacteria without exerting significant hemolytic activity. To investigate the modes of action of tested peptides 2 and 8 in antimicrobial and hemolytic activity, electrophysiological measurements were performed.

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