Calculation of Protein Conformation by the Build-up Procedure. Application to Bovine Pancreatic Trypsin Inhibitor Using Limited Simulated Nuclear Magnetic Resonance Data

Vásquez, Maximiliano; Scheraga, Harold A.

doi:10.1080/07391102.1988.10506425

Cited by 64 publications

(19 citation statements)

References 81 publications

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“…On the surface, this dissociation of sequence from structure would seem to create immense difficulties for fragment-based aspects of homology model building algorithms and for de novo structure prediction algorithms that exploit a buildup procedure (Vasquez & Scheraga, 1988) or secondary structure prediction methods. We suggest that the folding class of a protein provides a global constraint on the local conformation of these conformationally ambivalent peptides that favors a particular backbone geometry.…”

Section: Discussionmentioning

confidence: 99%

Origins of structural diversity within sequentially identical hexapeptides

1993

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Efforts to predict protein secondary structure have been hampered by the apparent structural plasticity of local amino acid sequences. Kabsch and Sander (1984, Proc. Natl. Acad. Sci. USA 81,[1075][1076][1077][1078] articulated this problem by demonstrating that identical pentapeptide sequences can adopt distinct structures in different proteins. With the increased size of the protein structure database and the availability of new methods to characterize structural environments, we revisit this observation of structural plasticity. Within a set of proteins with less than 50% sequence identity, 59 pairs of identical hexapeptide sequences were identified. These local structures were compared and their surrounding structural environments examined. Within a protein structural class ( d a , /3/& a/p, a + /I), the structural similarity of sequentially identical hexapeptides usually is preserved. This study finds eight pairs of identical hexapeptide sequences that adopt 6-strand structure in one protein and a-helical structure in the other. In none of the eight cases do the members of these sequence pairs come from proteins within the same folding class. These results have implications for class dependent secondary structure prediction algorithms.

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Section: Discussionmentioning

confidence: 99%

Origins of structural diversity within sequentially identical hexapeptides

1993

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“…Local energy minimization was carried out for each conformation by using a simplified force field based on a soft-sphere model (18) to remove atomic overlaps. No electrostatic term was included in these energy minimizations to avoid bias in the alignment of and E.…”

Section: Conversion Of the Native Structures From Flexible To Rigid Ementioning

confidence: 99%

On the orientation of the backbone dipoles in native folds

Ripoll

Vila

Scheraga

2005

Proc. Natl. Acad. Sci. U.S.A.

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The role of electrostatic interactions in determining the native fold of proteins has been investigated by analyzing the alignment of peptide bond dipole moments with the local electrostatic field generated by the rest of the molecule with and without solvent effects. This alignment was calculated for a set of 112 native proteins by using charges from a gas phase potential. Most of the peptide dipoles in this set of proteins are on average aligned with the electrostatic field. The dipole moments associated with ␣-helical conformations show the best alignment with the electrostatic field, followed by residues in ␤-strand conformations. The dipole moments associated with other secondary structure elements are on average better aligned than in randomly generated conformations. The alignment of a dipole with the local electrostatic field depends on both the topology of the native fold and the charge distribution assumed for all of the residues. The influences of (i) solvent effects, (ii) different sets of charges, and (iii) the charge distribution assumed for the whole molecule were examined with a subset of 22 proteins each of which contains <30 ionizable groups. The results show that alternative charge distribution models lead to significant differences among the associated electrostatic fields, whereas the electrostatic field is less sensitive to the particular set of the adopted charges themselves (empirical conformational energy program for peptides or parameters for solvation energy).charge distribution ͉ dipole moment ͉ electrostatics ͉ protein conformation C harge-charge and ionizable group-peptide dipole interactions have been proposed to play a relevant role in the stabilization of proteins (1) and in determining the native fold (2). Although a quantitative analysis of the relative stability of the native fold requires consideration of a delicate balance among all physical forces, we concentrate here on how electrostatic interactions can be identified as an important determination of the backbone conformation of the native structure.It is well known that the CO and NH dipoles in an ␣-helix are electrostatically aligned nearly parallel to the axis of the helix (3), and that the alignment of peptide dipoles in various types of secondary structure elements is significant in determining the 3D structure (4) and stability of globular proteins (5, 6). The concept of the preferential alignment of the backbone dipole moments ( ) with the local electrostatic field (E) (see Fig. 1) was used by Piela and Scheraga (7) and by Ripoll and Scheraga (8) to develop procedures to surmount the multiple-minima problem in the conformational analysis of peptides and proteins. The charges used in these procedures to define , shown in Fig. 1, are ECEPP͞3 (empirical conformational energy program for peptides) charges (9) that differ from other charges, e.g., PARSE (parameters for solvation energy) charges (10).Approximately 50% of the residues in proteins fit in the most common secondary structure classes (11), such as ␣-helix or...

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“…This procedure has been used to treat open-chain [13,15,19,20] and cyclic peptides [21,22] and fibrous proteins such as collagen [23][24][25]. Except for fibrous proteins, where advantage is taken of symmetry relations, the method becomes unmanageable for polypeptide chains containing more than about 20 amino acid residues.…”

Section: Applicationsmentioning

confidence: 99%

An approach to the multiple-minima problem in protein folding by relaxing dimensionality

Purisima

Scheraga

1987

Journal of Molecular Biology

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Abstract. Protein folding is a very difficult global optimization problem. Furthermore it is coupled with the difficult task of designing a reliable force field with which one has to search for the global minimum. A summary of a series of optimization methods developed and applied to various problems involving polypeptide chains is described in this paper. With recent developments, a computational treatment of the folding of globular proteins of up to 140 residues is shown to be tractable.

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Calculation of Protein Conformation by the Build-up Procedure. Application to Bovine Pancreatic Trypsin Inhibitor Using Limited Simulated Nuclear Magnetic Resonance Data

Cited by 64 publications

References 81 publications

Origins of structural diversity within sequentially identical hexapeptides

Origins of structural diversity within sequentially identical hexapeptides

On the orientation of the backbone dipoles in native folds

An approach to the multiple-minima problem in protein folding by relaxing dimensionality

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