What Differentiates Free Amino Acids and Aminoacyl Residues? An Exploration of Conformational and Lipophilicity Spaces

Testa, Bernard; Raynaud, Isabelle; Kier, Lemont B.

doi:10.1002/(sici)1522-2675(19990505)82:5<657::aid-hlca657>3.0.co;2-8

Cited by 12 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At this stage, it is worth mentioning that several lipophilicity (or inverse hydrophobicity) scales have been proposed for neutral amino acids and peptides. − A frequently used approach for assessing the lipophilicity of peptides is the development of additive models, whereby the entire lipophilicity of peptides is factored into contributions from molecular fragments (i.e., amino acid residues). Using this approach, Fujita et al used a set of 124 di- and tripeptides and tried to investigate whether their log P values could be calculated from the sum of the liphophilic increments of the amino acid residues.…”

Section: Introductionmentioning

confidence: 99%

Lipophilicity of Peptide Anions: An Experimental Data Set for Lipophilicity Calculations

Gulaboski

Scholz

2003

J. Phys. Chem. B

View full text Add to dashboard Cite

For the first time, the standard Gibbs energies of the transfer of peptide anions from aqueous solution to nitrobenzene were determined with the help of electrochemical measurements. These systematic studies clearly show that the lipohilicity contributions of single amino acid residues to the overall lipohilicity of a peptide anion strongly depend on the position of the amino acid in the backbone of the peptide. Therefore, additive models to calculate the overall lipophilicity of a peptide cannot provide very precise data. The present study is a plea for the experimental establishment of a data set that takes into account the individual nature of an amino acid residue and its position in a peptide.

show abstract

Section: Introductionmentioning

confidence: 99%

Lipophilicity of Peptide Anions: An Experimental Data Set for Lipophilicity Calculations

Gulaboski

Scholz

2003

J. Phys. Chem. B

View full text Add to dashboard Cite

show abstract

“…Indeed, the conformational behavior of side chains (the so-called 'Chi space') is an important determinant of the surface and recognition properties of proteins [17]. Preliminary studies using molecular dynamics (MD) simulations and analysis of three-dimensional (3D) molecular fields had shown that the property space of the central residue in tripeptides is indeed constrained compared to the free amino acid [18,19]. Here, we present an MD simulation of profilin Ib, a contractile protein of Acanthamoeba castellanii.…”

mentioning

confidence: 99%

Conformational constraints on side chains in protein residues increase their information content

Bojarski

Nowak

Testa

2003

Cellular and Molecular Life Sciences (CMLS)

View full text Add to dashboard Cite

Like all other complex biological systems, proteins exhibit properties not seen in free amino acids (i.e., emergent properties). The present investigation arose from the deduction that proteins should offer a good model to approach the reverse phenomenon, namely top-down constraints experienced by protein residues compared to free amino acids. The crystalline structure of profilin Ib, a contractile protein of Acanthamoeba castellanii, was chosen as the object of study and submitted to 2-ns molecular dynamics simulation. The results revealed strong conformational constraints on the side chain of residues compared to the respective free amino acids. A Shannon entropy (SE) analysis of the conformational behavior of the side chains showed in most cases a strong decrease in the SE of the chi1 and chi2 dihedral angles compared to free amino acids. This is equivalent to stating that conformational constraints on the side chain of residues increase their information content and hence recognition specificity compared to free amino acids. In other words, the vastly increased information content of a protein relative to its free monomers is embedded not only in the tertiary structure of the backbone, but also in the conformational behavior of the side chains. The postulated implication is that both backbone and side chains, by virtue of being conformationally constrained, contribute to the recognition specificity of the protein toward other macromolecules and ligands.

show abstract

“…With regard to local flexibility, MD simulations of the protein profilin Ib performed over 10 ns revealed large differences in the behavior of the side chains compared with the free amino acids, with their conformational space severely restricted and/or shifted to regions improbable in the free state [53,54]. The significant consequences of such constraints on side-chain recognition forces and interaction fields have not been sufficiently explored and deserve to be evaluated on a larger scale [55], also because such conformational constraints can contribute notably to protein recognition specificity towards other macromolecules and ligands as proposed by Loewenstein [56].…”

Section: Property Space and Biomacromoleculesmentioning

confidence: 99%

Chemodiversity and Molecular Plasticity: Recognition Processes as Explored by Property Spaces

Vistoli

Pedretti

Testa³

2011

Future Med. Chem.

Self Cite

View full text Add to dashboard Cite

In the last few years, a need to account for molecular flexibility in drug-design methodologies has emerged, even if the dynamic behavior of molecular properties is seldom made explicit. For a flexible molecule, it is indeed possible to compute different values for a given conformation-dependent property and the ensemble of such values defines a property space that can be used to describe its molecular variability; a most representative case is the lipophilicity space. In this review, a number of applications of lipophilicity space and other property spaces are presented, showing that this concept can be fruitfully exploited: to investigate the constraints exerted by media of different levels of structural organization, to examine processes of molecular recognition and binding at an atomic level, to derive informative descriptors to be included in quantitative structure--activity relationships and to analyze protein simulations extracting the relevant information. Much molecular information is neglected in the descriptors used by medicinal chemists, while the concept of property space can fill this gap by accounting for the often-disregarded dynamic behavior of both small ligands and biomacromolecules. Property space also introduces some innovative concepts such as molecular sensitivity and plasticity, which appear best suited to explore the ability of a molecule to adapt itself to the environment variously modulating its property and conformational profiles. Globally, such concepts can enhance our understanding of biological phenomena providing fruitful descriptors in drug-design and pharmaceutical sciences.

show abstract

What Differentiates Free Amino Acids and Aminoacyl Residues? An Exploration of Conformational and Lipophilicity Spaces

Cited by 12 publications

References 13 publications

Lipophilicity of Peptide Anions: An Experimental Data Set for Lipophilicity Calculations

Lipophilicity of Peptide Anions: An Experimental Data Set for Lipophilicity Calculations

Conformational constraints on side chains in protein residues increase their information content

Chemodiversity and Molecular Plasticity: Recognition Processes as Explored by Property Spaces

Contact Info

Product

Resources

About