Gn Ramachnadran History

G.N. Ramachandran

A Short Biography

One of the most accomplished biophysicists, who inspired generations in India

Oct 08, 1922 – April 07, 2001

Gopalasamudram Narayanan Ramachandran (G.N. Ramachandran) was a renowned biophysicist from India. GNR or Ram, as affectionately called by his friends and colleagues, is known for his triple contributions: (i) the discovery of the triple helical structure of collagen along with Gopinath Kartha in 1954, (ii) developing a two-dimensional map describing allowed states of protein structure, precisely speaking protein conformation (φ, ψ), along with his student Chandrasekharan Ramakrishnan (CR) and Vishwanathan Sasisekharan in 1963, what is popularly known as Ramachandran (φ, ψ) map, a simple and widely used tool for protein structure validation (checks) and analysis, and (iii) anomalous scattering to solve phase problem in protein structure determination using X-ray crystallography.

Initial Years (1922-1935)

He was born on 8 October 1922 in a small town of Ernakulam in the southernmost state of Kerala in India. He hailed from a well-educated brahmin (a Hindu caste associated with priesthood and religious scholarship) family. His father G. Narayana Iyer, was a professor of mathematics and the principal of a local Maharaja's college in Ernakulam town, who was instrumental in shaping GNR's intellectual orientation toward the science.

Higher Education (1936-1950)

Ramachandran completed intermediate from Maharaja's college and B.Sc. honours in Physics from St. Joseph's College, Tiruchirappalli in 1939. In 1942, he took admission in the department of Electrical Engineering at the Indian Institute of Science (IISc), Bangalore, but later switched to the Department of Physics and completed his master's and doctorate (DSc) in 1947 under the supervision of Nobel laureate Sir C. V. Raman. Subsequently, he went to the Cavendish Laboratory in the University of Cambridge and obtained his second doctorate (PhD) degree on X-ray diffuse scattering in 1949 in a very short span of 2-years under the supervision of Prof. William Alfred Wooster.

Golden Period at the University of Madras (1950-1970)

GNR returned to India in 1949 and joined at the Department of Physics, Indian Institute of Science, Bangalore as an Assistant Professor. In 1952, on invitation of Sir Arcot A. Lakshmanaswami Mudaliar, he moved to the Department of Physics in the University of Madras. Lakshmanaswami Mudaliar was then vice chancellor of university, who was a great institution builder and academic administrator. GNR became the founder head of the department just at the age of 29. This move from Bangalore to Madras marked the beginning of a golden period in Ramachandran's career, in particular, and molecular biology and biophysics research in India, in general.

First Major Contribution: Triple-helix Model of Collagen

In Madras, J.D. Bernal a well-known irish physicist and crystallographer then visited the university campus and advised GNR, a physicist by training, to work on the structures of biological macromolecules. Using X-ray diffraction, along with his first post-doctoral fellow Gopinath Kartha, he proposed a novel triple helical structure of collagen in 1954. X-ray diffraction (or crystallography) is a technique to visualize molecules of one-billionth of the size of a meter and Collagen is a protein occuring in the connective tissues of body such as skin, tendon and bone, which provide tensile strength. The structure of collagen was initially described by Pauling and Corey in 1951 but their proposed model lacked many critical details. GNR and Kartha refined this model and published in their two articles in 1954 and 55, which offered crucial insights into the Collagen sequence and its triple-helical coiled-coil structure. Around the same time in 1955, Alexander Rich and Francis Crick also published an article. They validated their model using Coven’s experiment (Coven, 1955). Their model by and large similar but the drawback they highlighted in GNR’s model was the number of hydrogen bonds for every three residues of the collagen helix: there were two in Ramachandran's model and one in Rich's model. (Sarma, 2001). But their main criticism was the presence of unusual short contacts in GNR model. Short contacts are overlaps of atomic spheres. Such close approach of two non-bonded atoms would be unrealistic due to electron-electron negative charge repulsion. The collagen discovery remained controversial. Many of the enigma in the science are resolved after efforts of several individuals and often it is hard to assign due credit to individuals. Even though GNR did not get due recognition for his collagen work, nevertheless his group had established their sound presence in the world. The science mostly dominated by west, had difficulty in pronouncing Indian names, and they identified GNR and team as the Madras Group, and designated the triple helical structure as Madras helix (Sasisekharan & Yathindra, 1999).

Second and Important Contribution: Ramachandran Map

Rich and Crick’s criticism of the GNR’s model was indeed a disappointment for Madras group. On the contrary it led to the birth of a new tool having profound implications for testing protein structures in modern biology. The collagen controversy led GNR and his two colleagues, Ramakrishnan and Sasisekharan to screen thousands of protein structures (precisely speaking protein conformations arising out of rotations about single bonds N-Cα and Cα–C in each of the amino acid units within a protein) that are free from unrealistic short atomic overlaps. They asked a simple yet profound question, what are allowed structures for proteins possessing no short contacts? Starting with a model peptide N-Acetyl-L-alanine N'-methylamide, and a simple concept of steric hindrance (i.e., no two atoms can come closer than the sum of their van der Waals radii) they began working out all possible conformation states of proteins and started classifying them as normally allowed and disallowed structures. At that time the only device available to them was a pocket calculator. C. Ramakrishnan was PhD student who was behind all this hard work. He would start each day with 8AM working tirelessly till night, totally absorbed in lengthy calculations for years. Eventually in 1963, they proposed a two-dimensional map of rotational angles  and , clearly depicting the allowed and disallowed states in protein structure. This demarcation of map into allowed and disallowed region indeed turned out to be very useful to check the validity of any new protein structure and this made it a popular tool in biochemistry. Soon after, the experimental proof of the Ramachandran map came, when Sir John Kendrew determined the world’s first structure of myoglobin. Ramachandran and coworkers were very excited to learn an impressive match between their theoretical map and experimental structure.

Recognitions and Awards

Major Honors:
  • Fellow of the Royal Society (FRS) - 1977
  • International Union of Crystallography Ewald Prize - 1999
  • Shanti Swarup Bhatnagar Award - 1961
  • Nobel Prize Nomination

Unfortunately, unlike many of the scientists of his stature, he did receive much recognition and even worse in India he was poorly recognized with sole exception of the Shanti Swarup Bhatnagar award for mid age scientist awarded in 1961. He was not even awarded a Padma Shri, the covetous Padma awards given every year for excellence by Indian Government. There is reason behind this. He was a down -to-earth scientist in a true sense, and completely absorbed himself in academics alone. He never lobbied, nor he ever relished administrative positions. Add to that, like a true perfectionist trait of many of the scientists, he expected to see his surrounding people to be as intelligent and dedicatied as he was, and on a number of occasions he failed to maintain his temperament in the lab (Mohanti, 2012).

Massive Growth of Molecular Biophysics Research (1971-1989)

Once vice chancellor Mudaliar was out in 1969, there was gradual decline of the academic standards in University. GNR, unhappy and unused with this type of work-culture in academics, decided to move out of University of Madras. He resigned from Madras in 1970 and went to University of Chicago in the Biophysics Department as a visiting professor. At Chicago, he developed a novel method to reconstruct three-dimensional images from two-dimensional data, which laid the the foundation for computerized tomography. He returned to the Indian Institue of Science in 1971 and established a department called Molecular Biophysis Unit (MBU), which in subsequent years became a prominant place for biophysical research. Most of the GNR’s contribution were made at University of Madras. His term at MBU was relatively lacklustre. His contribution during his stay at IISc were mostly in crystallography, such as anomalous dispersion for solving phase problems required in protein structure determination and X-ray intensities statistics. However, this was a period which witnessed massive growth and promotion of biological research in the country. IISc became a hot seat of molecular biology and biophysics research that would continue to lead science in the country in years to come. He was a great example of science, academic, institution and nation builder. GNR retired from service in 1978 but continued as a Professor of mathematical philosophy until 1989. He stopped working due to slow growth of Parkinson’s disease, which did not allow him to work properly.

Difficult Period Towards End (1989-2001)

Ailing GNR and his wife Rajalakshmi decied to move to the Institute of Plasma Research, Gandhinagar to leave peaceful retirement life with one of their son Hari, who was then working as Scientist at the Institute. But contrary to their wish, couple of exotic factors like lack of communication in local langauage and quite away from active research life that he was accoustomed to all along, might have contributed to deterioration of his health. Common in traditional indian family, GNR was cared for by his wife ever since he married in 1945. This made him completely worry free from many day to day responsibilities of house. At that juncture, his destiny took an ugly turn and in July 1998, Rajalakshmi suffered a cardiac arrest and died. Ramachandran himself was handicapped due to Parkinson, the departure of his 50 year old companion turned out to be a double blow. Later he suffered a stroke and thereafter, he moved to Chennai. Since August 1999, Ramachandran was under nursing care in a hospital in Madras and on 7th April, 2001 at the ripe age of 78 he died of cardiac arrest in the hospital. He survived by two sons, Hari (professot at IIT madras), Ramesh (Professor of Astrophysics at Harvard University) and, and a daughter, Vijaya (Professor of Computer Science, University of Texas at Austin) (Mohanti, 2012).

A Karmayogi in True Sense

Today Ramachandran map is an indispensable tool in the study of molecular structures and regularly taught to students in biochemistry subject. It is widely used tool for protein structure validation and model building. His work and life inspired generations. Ramachandran in his scientific career spanning sixty years left a strong leagacy of robust and thriving structural biology group in India. His scientific discoveries, personalities, his life continue to inspire scientists, and remain topic of discussion.

References

Books & Biographies:
Research Papers:
  • Ramachandran, G. N., & Kartha, G. (1954). Structure of Collagen. Nature, 174(4423), 269–270
  • Srinivasan N. Chandrasekharan Ramakrishnan (1939–2019): The student behind the Ramachandran map. Protein Sci. 2019
Digital Resources:
  • Nature volume 411, page 544 (2001) - M. Vijayan
  • Nature Structural Biology volume 8, pages 489–491 (2001)
  • Structure, Volume 9, Issue 9, 765 – 767, 2001 - Raghupathy Sarma