Ab initio conformational analysis of N -formyl l -alanine amide including electron correlation

Yu, Ching-Hsing; Norman, Mya A.; Schäfer, Lothar; Ramek, Michael; Peeters, Anik; Alsenoy, C. Van

doi:10.1016/s0022-2860(01)00565-8

Cited by 35 publications

(51 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and less typical structural motifs (e.g., loops, ␤-bulges) of a single peptide chain are more and more in the focus of computational studies. [1][2][3][4][5][6][7][8][9][10] Properties associated with the above molecular conformers are commonly classified either by structure or stability characteristics. Stability is an energetic concept measurable by the computed total energy, often transformed to some relative energy with respect to a reference state.…”

Section: Stability Measures Of Systems With Covalently Bonded Peptidementioning

confidence: 99%

Stability issues of covalently and noncovalently bonded peptide subunits

et al. 2004

View full text Add to dashboard Cite

Abstract:The present study focuses on important questions associated with modeling of peptide and protein stability.Computing at different levels of theory (RHF, B3LYP) for a representative ensemble of conformers of di-and tripeptides of alanine, we found that the Gibbs Free Energy values correlate significantly with the total electronic energy of the molecules (0.922 Յ R 2 ). For noncovalently attached but interacting peptide subunits, such as [For-NH 2 ] 2 or [For-L-Ala-NH 2 ] 2 , we have found, as expected, that the basis set superimposition error (BSSE) is large in magnitude for small basis set but significantly smaller when larger basis sets [e.g., B3LYP/6-311ϩϩG(d,p)] are used. Stability of the two hydrogen bonds of antiparallel ␤-pleated sheets were quantitatively determined as a function of the molecular structure, S10 and S14, computed as 4.0 Ϯ 0.5 and 8.1 Ϯ 1.1 kcal/mol, respectively. Finally, a suitable thermoneutral isodesmic reaction was introduced to scale both covalently and noncovalently attached peptide units onto a common stability scale. We found that a suitable isodesmic reaction can result in the total electronic energy as well as the Gibbs free energy of a molecule, from its "noninteracting" fragments, as accurate as a few tenths of a kcal per mol. The latter observation seems to hold for peptides regardless of their length (1 Յ n Յ 8) or the level of theory applied.

show abstract

Section: Stability Measures Of Systems With Covalently Bonded Peptidementioning

confidence: 99%

Stability issues of covalently and noncovalently bonded peptide subunits

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Using Quantum Mechanics-based potentials, it has already been proved in small peptides that, for a given choice of constrained coordinates, their equilibrium values do depend on the conformation s significantly [119,48,120,121]. In this work, we will show en passant, as some previous works have already done [49,58,122,41,50], that the functions f (s) also depend on s in the case of the much simpler classical force fields [16,17,18,19,20,21] typically used for MD of proteins and nucleic acids.…”

Section: Flexible Vs Hard Constraintsmentioning

confidence: 70%

The canonical equilibrium of constrained molecular models

Echenique

Cavasotto

García-Risueño

2011

Eur. Phys. J. Spec. Top.

View full text Add to dashboard Cite

Abstract. In order to increase the efficiency of the computer simulation of biological molecules, it is very common to impose holonomic constraints on the fastest degrees of freedom; normally bond lengths, but also possibly bond angles. Since the maximum time step required for the stability of the dynamics is proportional to the shortest period associated with the motions of the system, constraining the fastest vibrations allows to increase it and, assuming that the added numerical cost is not too high, also increase the overall efficiency of the simulation. However, as any other element that affects the physical model, the imposition of constraints must be assessed from the point of view of accuracy: both the dynamics and the equilibrium statistical mechanics are model-dependent, and they will be changed if constraints are used. In this review, we investigate the accuracy of constrained models at the level of the equilibrium statistical mechanics distributions produced by the different dynamics. We carefully derive the canonical equilibrium distributions of both the constrained and unconstrained dynamics, comparing the two of them by means of a "stiff" approximation to the latter. We do so both in the case of flexible and hard constraints, i.e., when the value of the constrained coordinates depends on the conformation and when it is a constant number. We obtain the different correcting terms associated with the kinetic energy mass-metric tensor determinants, but also with the details of the potential energy in the vicinity of the constrained subspace (encoded in its first and second derivatives). This allows us to directly compare, at the conformational level, how the imposition of constraints changes the thermal equilibrium of molecular systems with respect to the unconstrained case. We also provide an extensive review of the relevant literature, and we show that all models previously reported can be considered special cases of the most general treatments presented in this work. Finally, we numerically analyze a simple methanol molecule in order to illustrate the theoretical concepts in a practical case.

show abstract

“…Although coupled cluster [14,31] and MP4 [30] methods have been used to perform single-points on top of the geometries optimized at lower levels for some selected conformers 3 , the highest homolevels used to calculate full PESs in the literature after the one used in this study seem to be MP2/6-311G(d,p) in ref. 28 and B3LYP/6-311++G(d,p) in ref. 31 (assuming that the accuracy of the B3LYP method lies somewhere between RHF and MP2).…”

Section: Mp2//mp2-intramethods Model Chemistriesmentioning

confidence: 99%

“…This is why, the most frequently studied peptides are the shortest ones: the dipeptides [13][14][15][16][17], in which a single amino acid residue is capped at both the N-and C-termini with neutral peptide groups. Among them, the most popular choice has been the alanine dipeptide [9,14,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], which, being the simplest chiral residue, shares many similarities with most of the rest of dipeptides for the minimum computational price.…”

Section: Introductionmentioning

confidence: 99%

Efficient model chemistries for peptides. I. General framework and a study of the heterolevel approximation in RHF and MP2 with Pople split‐valence basis sets

Echenique

Alonso

2008

J Comput Chem

View full text Add to dashboard Cite

We present an exhaustive study of more than 250 ab initio potential energy surfaces (PESs) of the model dipeptide HCO-L-Ala-NH2. The model chemistries (MCs) used are constructed as homo-and heterolevels involving possibly different RHF and MP2 calculations for the geometry and the energy. The basis sets used belong to a sample of 39 selected representants from Pople's split-valence families, ranging from the small 3-21G to the large 6-311++G(2df,2pd). The reference PES to which the rest are compared is the MP2/6-311++G(2df,2pd) homolevel, which, as far as we are aware, is the more accurate PES of a dipeptide in the literature. The aim of the study presented is twofold: On the one hand, the evaluation of the influence of polarization and diffuse functions in the basis set, distinguishing between those placed at 1st-row atoms and those placed at hydrogens, as well as the effect of different contraction and valence splitting schemes. On the other hand, the investigation of the heterolevel assumption, which is defined here to be that which states that heterolevel MCs are more efficient than homolevel MCs. The heterolevel approximation is very commonly used in the literature, but it is seldom checked. As far as we know, the only tests for peptides or related systems, have been performed using a small number of conformers, and this is the first time that this potentially very economical approximation is tested in full PESs. In order to achieve these goals, all data sets have been compared and analyzed in a way which captures the nearness concept in the space of MCs. * Corresponding author. E-mail address: pnique@unizar.es 1The most important results of the study are the following: First, that the convergence in method is not achieved in the RHF → MP2 step. Second that the transferability of basis set accuracy from RHF to MP2 is imperfect. These two conclusions lead us to discourage the use of RHF MCs for peptides. Regarding the relative efficiency of the Pople's basis sets, we recommend the inclusion of polarization functions in 1st-row atoms and we discourage the use of basis sets containing doubly-split polarization shells and no diffuse functions. Also, we have found that 6-31G(d) is very efficient for calculating the geometry, and that both the RHF and MP2 infinite basis set limits are approximately reached at 6-311++G(2df,2pd). Finally, related to the heterolevel approximation, we conclude that it is essentially correct for the description of the conformational behaviour of HCO-L-Ala-NH2 both at RHF and MP2. Nevertheless, we place a cautionary remark on the use of RHF geometries with MP2 single-points: Whereas this practice could be accurate enough for short peptides, the accumulation of errors may render it unreliable for longer chains and require the use of MP2 geometries.

show abstract

Ab initio conformational analysis of N -formyl l -alanine amide including electron correlation

Cited by 35 publications

References 65 publications

Stability issues of covalently and noncovalently bonded peptide subunits

Stability issues of covalently and noncovalently bonded peptide subunits

The canonical equilibrium of constrained molecular models

Efficient model chemistries for peptides. I. General framework and a study of the heterolevel approximation in RHF and MP2 with Pople split‐valence basis sets

Contact Info

Product

Resources

About