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Chair Conformation of Cyclohexane

Chair Conformation of Cyclohexane

The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...

The Equilibrium Binding Constant and Binding Strength

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:

The Equilibrium Binding Constant and Binding Strength

The Equilibrium Binding Constant and Binding Strength

Conformations of Cyclohexane

Conformations of Cyclohexane

Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...

Molecular Models

Molecular Models

Physical models representing molecular architectures of chemical compounds play essential roles in understanding chemistry. The use of molecular models makes it easier to visualize the structures and shapes of atoms and molecules.

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...

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Related Experiment Video

Updated: Jan 3, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Modelling the binding mode of macrocycles: Docking and conformational sampling.

Sarah J Martin¹, I-Jen Chen², A W Edith Chan¹

¹Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.

Bioorganic & Medicinal Chemistry

|November 28, 2019

Summary

Predicting macrocycle binding modes is challenging. Tailored docking protocols, using extensive conformer ensembles, significantly improve success rates for macrocycle drug discovery.

Keywords:

Computational chemistry Conformers Docking Drug discovery Macrocycle Molecular recognition

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Published on: March 1, 2022

Area of Science:

Medicinal Chemistry
Computational Chemistry
Structural Biology

Background:

Drug discovery faces challenges with shallow protein binding sites, often targeted by macrocycles.
Macrocycles are promising drug candidates but their complex structures pose computational challenges for binding mode prediction.
Knowledge of macrocycle binding modes is crucial for drug design, especially when X-ray crystallography data is limited.

Purpose of the Study:

To investigate the efficacy of the GOLD docking software and ChemPLP scoring for macrocycle binding mode prediction.
To evaluate the impact of conformational sampling on macrocycle docking accuracy.
To develop improved computational protocols for macrocycle docking.

Main Methods:

Curated a test set of 41 protein-macrocycle X-ray structures.
Performed rigid docking of known bioactive conformers.
Assessed GOLD's built-in conformational search versus docking extensive conformer ensembles.
Analyzed reasons for docking failures (sampling vs. scoring).

Main Results:

Rigid docking of known conformers achieved 92.7% success without conformational search.
GOLD's built-in conformational search yielded only 29.3% success.
Docking success rate increased to 58.5% when GOLD was provided with extensive conformer ensembles docked rigidly.
Identified sampling and scoring as key factors influencing macrocycle docking accuracy.

Conclusions:

Macrocycle binding mode prediction remains a significant challenge in computational drug discovery.
Tailored docking protocols, particularly those incorporating extensive conformational sampling, can substantially enhance prediction accuracy.
Further research into the interplay of conformational sampling and scoring functions is essential for advancing macrocycle modeling.