Correction of cavity-induced errors in polarization charges of continuum solvation models

Abstract:We have studied the influence of implicit solvent models, inclusion of explicit water molecules, inclusion of vibrational effects, and density functionals on the quality of the predicted pK a of small amino acid sidechain models. We found that the inclusion of vibrational effects and explicit water molecules is crucial to improve the correlation between the computed and the experimental values.However, achieving convergence of the results requires the addition of too many explicit water molecules, which generate new problems related to the presence of multiple minima in the potential energy surface. It thus appears that a satisfactory ab initio prediction of amino acid sidechain pK a will require methods that fully sample the potential energy surface in the presence of large solvation shells, while at the same time computing vibrational contributions to the enthalpy and entropy of the system under study in all points of that surface. Pending development of efficient algorithms for those computations, we strongly suggest that whenever abnormal protonation states are found in a computational study the reaction profile should be computed under the each of the different protonation micro-states by constraining the relevant N-H or O-H bonds, in order to avoid artifacts inherent to the complex nature of the factors contributing to the pK a .

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“…37,38 in Firefly and C-PCM 39,40 in Gamess (US)). Average DFT solvation energies were used as estimates of MP2 solvation energies.…”

Section: Methodsmentioning

confidence: 99%

Improving the study of proton transfers between amino acid side chains in solution: choosing appropriate DFT functionals and avoiding hidden pitfalls

et al. 2012

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“…All energy values described in the text include solvation effects (ε=10) computed using the Polarizable Continuum Model (Tomasi & Persico, 1994;Mennucci & Tomasi, 1997;Cossi et al, 1998) implemented in Firefly. ε=10 was chosen instead of the more common ε=4 to model some of the stabilization of the ionic forms of Asp274 and propionic acid residues provided in the enzyme by hydrogen bonding with the Gly409-Leu410 backbone amide.…”

Section: Methodsmentioning

confidence: 99%

With or without light: comparing the reaction mechanism of dark-operative protochlorophyllide oxidoreductase with the energetic requirements of the light-dependent protochlorophyllide oxidoreductase

Silva

2014

Preprint

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View the peer-reviewed version (peerj.com/articles/551), which is the preferred citable publication unless you specifically need to cite this preprint.Silva PJ. 2014. With or without light: comparing the reaction mechanism of dark-operative protochlorophyllide oxidoreductase with the energetic requirements of the light-dependent protochlorophyllide oxidoreductase.PeerJ 2:e551 https://doi.org/10.7717/peerj.551 Wi t h o r wi t h o u t l i g h t : c o mp a r i n g t h e r e a c t i o n me c h a n i s m o f d a r k -o p e r a t i v e p r o t o c h l o r o p h y l l i d e o x i d o r e d u c t a s e wi t h t h e e n e r g e t i c r e q u i r e me n t s o f t h e l i g h t -d e p e n d e n t p r o t o c h l o r o p h y l l i d e o x i d o r e d u c t a s eT h e a d d i t i o n o f t wo e l e c t r o n s a n d t wo p r o t o n s t o t h e C 1 7 = C 1 8 b o n d i n p r o t o c h l o r o p h y l l i d e i s c a t a l y z e d b y a l i g h t -d e p e n d e n t e n z y me r e l y i n g o n NA DP H a s e l e c t r o n d o n o r , a n d b y a l i g h ti n d e p e n d e n t e n z y me b e a r i n g a ( Cy s ) 3 A s p -l i g a t e d [ 4 F e -4 S ] c l u s t e r wh i c h i s r e d u c e d b y c y t o p l a s mi c e l e c t r o n d o n o r s i n a n A T P -d e p e n d e n t ma n n e r a n d t h e n f u n c t i o n s a s e l e c t r o n d o n o r t o p r o t o c h l o r o p h y l l i d e . T h e p r e c i s e s e q u e n c e o f e v e n t s o c c u r r i n g a t t h e C 1 7 = C 1 8 b o n d h a s n o t , h o we v e r , b e e n d e t e r mi n e d e x p e r i me n t a l l y i n t h e d a r k -o p e r a t i n g e n z y me . I n t h i s p a p e r , we p r e s e n t t h e c o mp u t a t i o n a l i n v e s t i g a t i o n o f t h e r e a c t i o n me c h a n i s m o f t h i s e n z y me a t t h e B 3 L Y P / 6 -3 1 1 + G( d , p ) / / B 3 L Y P / 6 -3 1 G( d ) l e v e l o f t h e o r y . T h e r e a c t i o n me c h a n i s m b e g i n s wi t h s i n g l e -e l e c t r o n r e d u c t i o n o f t h e s u b s t r a t e b y t h e ( Cy s ) 3 A s p -l i g a t e d [ 4 F e -4 S ] , y i e l d i n g a n e g a t i v e l y -c h a r g e d i n t e r me d i a t e . De p e n d i n g o n t h e r a t e o f F e -S c l u s t e r r e -r e d u c t i o n , t h e r e a c t i o n e i t h e r p r o c e e d s t h r o u g h d o u b l e p r o t o n a t i o n o f t h e s i n g l e -e l e c t r o n -r e d u c e d s u b s t r a t e , o r b y a l t e r n a t i n g p r o t o n / e l e c t r o n t r a n s f e r . T h e c o mp u t e d r e a c t i o n b a r r i e r s s u g g e s t t h a t F e -S c l u s t e r r e -r e d u c t i o n s h o u l d b e t h e r a t e -l i mi t i n g s t a g e o f t h e p r o c e s s . P o i s s o n -B o l t z ma n n c o mp u t a t i o n s o n t h e f u l l e n z y me -s u b s t r a t e c o mp l e x , f o l l o we d b y Mo n t e Ca r l o s i mu l a t i o n s o f r e d o x a n d p r o t o n a t i o n t i t r a t i o n s r e v e a l e d a h i t h e r t o u n s u s p e c t e d p H-d e p e n d e n c e o f t h e r e a c t i o n p o t e n t i a l o f...

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“…were computed by applying the polarizable conductor model 15,16,17 , as implemented in PcGamess 18 , on gas-phase optimized geometries. All solution energies presented include electrostatic and cavitation energies.…”

Section: Methodsmentioning

confidence: 99%

Computational Studies on the Reactivity of Substituted 1,2-Dihydro-1,2-azaborines

Silva¹,

Ramos²

2009

J. Org. Chem.

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Abstract:We have investigated important intermediates of electrophilic aromatic substitution reactions and one-electron oxidation of substituted 1,2-dihydro-1,2-azaborines with density-functional theory. The results show that electrophilic substitution reactions and one-electron oxidation of substituted 1,2-azaborines are generally much more favorable than those of the corresponding benzene derivatives.Both chlorination and nitration of several boron-unsubstituted 1,2-azaborines are expected to break the boron-hydrogen bond, yielding boron-chlorinated 1,2-azaborines and a novel class of boronbound 1,2-azaborinyl nitrites, respectively. Comparison between the relative stabilities of C 3 -bound and C 5 -bound Wheland intermediates of different electrophilic substitution reactions of 1,2-azaborines further suggests that the preference of the C 3 -over C 5 -substitution decreases with decreasing electrophilicity of the attacking group.

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Correction of cavity-induced errors in polarization charges of continuum solvation models

Cited by 80 publications

References 20 publications

Improving the study of proton transfers between amino acid side chains in solution: choosing appropriate DFT functionals and avoiding hidden pitfalls

Improving the study of proton transfers between amino acid side chains in solution: choosing appropriate DFT functionals and avoiding hidden pitfalls

With or without light: comparing the reaction mechanism of dark-operative protochlorophyllide oxidoreductase with the energetic requirements of the light-dependent protochlorophyllide oxidoreductase

Computational Studies on the Reactivity of Substituted 1,2-Dihydro-1,2-azaborines

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