The Ramachandran Map

Today, protein science has grown into the disciplines of protein engineering and protein design. The Ramachandran Plot gives us the geometrical constraints on the structure of each type of amino acid as it sits in its place on the protein chain. GNR’s originality in conceiving this physical chemistry study of and developing the quantitative limits to the conformational flexibility of each amino acid gave protein science the law-like behaviours of these subunits. This work is essential to all structural biology methods and computational methods in protein science and protein engineering. In this page we tell the story and explain the concepts involved.

Why a new criteria for protein structure validation was needed

The shortcomings of the van der Waals criteria for validating proteins

The Madras Triple Helix was declared unsatisfactory based on seemingly reasonable physical principles. However, Ramachandran and his team decided to challenge these principles. What led them to take such a bold step? V Sasisekharan, co-creator of the Ramachandran map, provides the reasoning for this along with N Srinivasan, Manju Bansal and P Balaram.

The alpha helix model under the hard-sphere assumption

Why does the Alpha helix, the most abundantly found secondary structure in proteins, have short contacts according to the van der Waals criteria for stability? What factors within the alpha helix allow it to be stable despite having steric clashes under the van der Waals criteria? George Rose explains.

The conception and development of the phi-psi map

The experiments that resulted in the phi-psi plot

How could torsion angles be used to measure distances between atoms? N Srinivasan, Manju Bansal and V Sasisekharan take us through the experimental design to define the new criteria of short contacts.

How C Ramakrishnan completed the calculations

Alongside the original insights about protein structure, the development of the Ramachandran map required a lot of tedious work. Today, complex computer softwares can carry out simulations of the kind that produced the map. But how did Ramachandran’s team manage this manually back in the 60s? N Srinivasan describes the amount of work behind the map and how his mentor, C Ramakrishnan, completed it.

Utility of the map to navigate protein structures

The conceptual breakthrough thanks to the Ramachandran map

George Rose is a protein biophysicist who has studied and worked on the Ramachandran map extensively. Here, he describes his fascination for the map, and why it was groundbreaking as a concept and a tool for protein scientists.

How the Ramachandran map would be used

What makes the Ramachandran map useful to scientists trying to solve protein structures? Venki Ramakrishnan describes how he and other protein scientists use it. N Srinivasan, George Rose and P Balaram talk about features that make it useful.

Ramachandran map - a simple, elegant theory that explains a lot

From an abstract idea to a fundamental framework

Initial reception of the map by Structural Biologists

The 1960s and 70s would see the first few protein structures that were solved, which coincided with the first uses of the Ramachandran map. P Balaram, Venki Ramakrishnan, Manju Bansal and Tom Blundell provide perspectives on the early reactions to the Ramachandran map by structural biologists.

The first protein structure validated by the map

A key event in the gradual acceptance of the map was the first protein structure (apart from collagen) that was tested by the Ramachandran map. N Srinivasan and Manju Bansal describe how this event came about and what this meant for the Madras group.

Validation of the Ramachandran and Kartha model of collagen

The Ramachandran map was originally conceived to validate the collagen structure by Ramachandran and Kartha. N Srinivasan and Manju Bansal talk about the extent to which the map helped in answering the ‘short-contacts’ criticism.

1965 Gordon conference

How the Ramachandran map was useful in solving the structure of insulin

The structure of insulin, solved in 1969 by Dorothy Hodgkin’s group in Oxford, was one of the first protein structures solved. Tom Blundell recalls how their team was helped by the Ramachandran map. He also describes how his future work on insulin evolution and dynamics was guided by the map.

Beta turns or Venkatachalam turns

Key events in structural biology that led to wider use of the map

P Balaram describes two technological advances that led to more protein structures being solved, and hence wider use of the map.

Unforeseen applications of the Ramachandran map

When asked the question about how the Ramachandran map has aged over the years, our experts share that a surprising number of relevant discoveries have made the map relevant time and again. What are these discoveries and fields of research? P Balaram, Andrej Sali and K N Ganesh elaborate.

Tom Blundell recalls how the Ramachandran map was useful for early protein softwares

Tom Blundell, one of the pioneers in structural bioinformatics, explains how the Ramachandran map played a role in some of his early works in structural bioinformatics.

Modeller

One of the most celebrated softwares created in structural bioinformatics is the program Modeller by Tom Blundell, Andrej Sali and their team. During the course of evolution, changes that occur in genetic sequences lead to changes in protein sequences and their structures. This is what modelling homology follows. Tom Blundell and Andrej Sali explain the role of the Ramachandran map in developing Modeller .

Can the Ramachandran map be considered as an example of Structural Bioinformatics?

Bioinformatics gained popularity as an established field in the 1980s and 90s. But could the Ramachandran map be considered a work in bioinformatics? Andrej Sali and Ken Ganesh make a case for this argument.

Molecular mechanics force fields

Protein conformations also change during the course of its activity in our cells everyday. The field of protein dynamics emerged was the subject of the Nobel prize in 2013. Tom Blundell, Andrej Sali and P Balaram discuss how the Ramachandran map served as its foundation.

Ramachandran map: a major validation tool in the PDB

As protein structures grew, people realized that a platform to view, review and access new protein structures was necessary. It would become near impossible to have cross-talk between labs like the one that happened around the structure of collagen. This led to the formation of databases like the Protein Data Bank for proteins and other biological structures. How did this affect the use of the map? N Srinivasan, Manju Bansal, Tom Blundell and Venki Ramakrishnan explain.

A rare fundamental theory in biology