Quantification of Conformational Entropy Unravels Effect of Disordered Flanking Region in Coupled Folding and Binding

SummaryGlycoprotein CD36, also known as GPIIIb or GPIV, is a major platelet glycoprotein that bears the newly identified Naka alloantigen. The aim of this study was to clone platelet CD36 and investigate other forms of CD36-cDNA present in monocytes, endothelial and HEL cells. RNA from above mentioned cells were reverse transcribed (RT), using specific primers for CD36, and amplified by the polymerase chain reaction (PCR) technique. Sequencing the different amplified platelet derived cDNA fragments, spanning the whole coding and flanking regions, showed the near identity between platelet and CD36-placenta cDNA. Platelet CD36-cDNA cross-hybridized, in Southern blots, with RT-PCR amplified cDNA originating from monocytes, endothelial and HEL cells. However, monocytes showed a RT-PCR amplified cDNA fragment (561 bp) that was present in platelets and placenta but not on endothelial on HEL-cells. Northern blot analysis of platelet RNA hybridized with placenta CD36 indicated the presence of a major (1.95 kb) and a minor (0.95 kb) transcript. The 1.95 kb transcript was the only one observed on Northern blots of monocytes, endothelial and HEL cells. These results indicate that the structure of CD36 expressed in platelets is similar, with the exception of the 3’ flanking region, to that of placenta. Differences in apparent molecular weight between CD36 and CD36-like glycoproteins may be due to post-translational modifications.

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Lack of association of the polymorphic locus in the 5'-flanking region of the human insulin gene and diabetes in American blacks

Diabetes ◽

10.2337/diabetes.34.5.433 ◽

1985 ◽

Vol 34 (5) ◽

pp. 433-439 ◽

Cited By ~ 17

Author(s):

S. Elbein ◽

P. Rotwein ◽

M. A. Permutt ◽

G. I. Bell ◽

N. Sanz ◽

...

Keyword(s):

Human Insulin ◽

Polymorphic Locus ◽

Insulin Gene ◽

Human Insulin Gene ◽

Flanking Region ◽

American Blacks

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Understanding Conformational Entropy in Small Molecules

10.26434/chemrxiv.12671027 ◽

2020 ◽

Author(s):

Lucian Chan ◽

Garrett Morris ◽

Geoffrey Hutchison

Keyword(s):

Small Molecules ◽

Degrees Of Freedom ◽

Absolute Error ◽

Low Energy ◽

Standard Entropy ◽

Free Energies ◽

Conformational Entropy ◽

Wide Range ◽

High Degree ◽

Empirical Corrections

The calculation of the entropy of flexible molecules can be challenging, since the number of possible conformers grows exponentially with molecule size and many low-energy conformers may be thermally accessible. Different methods have been proposed to approximate the contribution of conformational entropy to the molecular standard entropy, including performing thermochemistry calculations with all possible stable conformations, and developing empirical corrections from experimental data. We have performed conformer sampling on over 120,000 small molecules generating some 12 million conformers, to develop models to predict conformational entropy across a wide range of molecules. Using insight into the nature of conformational disorder, our cross-validated physically-motivated statistical model can outperform common machine learning and deep learning methods, with a mean absolute error ≈4.8 J/mol•K, or under 0.4 kcal/mol at 300 K. Beyond predicting molecular entropies and free energies, the model implies a high degree of correlation between torsions in most molecules, often as- sumed to be independent. While individual dihedral rotations may have low energetic barriers, the shape and chemical functionality of most molecules necessarily correlate their torsional degrees of freedom, and hence restrict the number of low-energy conformations immensely. Our simple models capture these correlations, and advance our understanding of small molecule conformational entropy.

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