50 years of collagen triple helix: a celebration of science

A tribute to G. N. Ramachandran

G. N. Ramachandran (GNR) was an outstanding crystallographer and structural biologist. The model of collagen he developed has stood the test of time and has contributed greatly to understanding the role of this important fibrous protein. His pioneering contributions in crystallography, particularly in relation to methods of structure analysis using Fourier techniques and anomalous dispersion, are well recognized. The Ramachandran plot remains the simplest and most commonly used descriptor and tool for the validation of protein structures. He received many prizes, including the 1999 Ewald Prize of the IUCr.

Hia first major contribution to structural biology was the proposal, made along with Gopinath Kartha, of the triple helical structure of the fibrous protein collagen. The proposal was published in Nature in 1954. A symposium entitled '50 years of triple helix: a celebration of science' was organized by S.K. Brahmachari, M. Bansal, and T. Ramasami in New Delhi on August 7, 2004, to commemorate the 50th anniversary of this event. The symposium and and the production of a documentary on the life and work of GNR, were supported by the Council of Scientific and Industrial Research (CSIR) and the Dept. of Science & Technology (DST). R.A. Mashelkar, Director General of CSIR, gave the keynote address. Taking examples from his own research on polymers, he emphasized the importance of being alert to deal with unanticipated and unusual results. V.S. Ramamurthy, Secretary, DST, presided over the inaugural function.

Three of the speakers were former students of Ramachandran. M. Bansal, his last graduate student, worked on the role of hydroxyproline in collagen and traced the history of the discovery of the coiled coil triple helical structure of collagen. The way Ramachandran and Kartha, working in virtual isolation at the U. of Madras, conceptualized the collagen model using scanty biochemical and Xray data, was truly remarkable. Her own work led to the appreciation of water-mediated hydrogen bonds involving hydroxyproline.

C. Ramakrishnan, a co-architect of the Ramachandran plot, then described how the controversy regarding the so-called short inter-atomic distances in the collagen model structure, led to a thorough examination by the GNR group of the minimum permitted distances between different non-bonded atoms. From crystal structure data, they were found to be considerably less than the sums of the appropriate van der waals radii. This re-examination led to the Ramachandran plot which graphically illustrates the restrictions on polypeptide conformation. This was at a time when the structure of only one globular protein had been determined. Now, after forty years and thousands of structure determinations, the Ramachandran plot remains a very important tool for describing and validating protein structures.

A.S. Kolaskar, another student, discussed the contribution of Ramachandran to the development of computational biology and bioinformatics. His own work with GNR was concerned with the non-planarity of the peptide unit consequent to the pyramidal nature of the amide nitrogen. The non-planarity was established through quantum chemical calculations and analysis of crystal structure data.

M. Vijayan, former head of the Molecular Biophysics Unit (MBU) established by GNR at the Indian Inst. of Science, Bangalore, dealt with the GNR legacy in crystallography. He referred to GNR's contribution to the use of anomalous dispersion for structure analysis. Much of Ramachandran's contributions were theoretical or computational in nature. He was keen on initiating biological macromolecular crystallography in India, but it could not be done during his active professional life. However, he lived to see the MBU, one of the two schools he established, play a leadership role in the development of macromolecular crystallography in India.

The Central Leather Research Inst. (CLRI), Chennai (formerly Madras), is situated next to the laboratory in which GNR worked during the 1950s and the 1960s. The original sample of collagen used by GNR in his X-ray diffraction experiments was in fact supplied by CLRI. The current Director of CLRI, T. Ramasami, described this association as well as currently available collagenbased materials, particularly those developed at his own Institute. A large number of diseases associated with collagen malfunctioning have been identified. The presentation of D. Balasubramanian was concerned with these diseases while S.S. Sriramachari spoke on diseases related to the effect of dietary protein on collagen.

The last scientific session was related to genomics. H. Yang (Beijing Genomics Inst.) gave an overview of the activity in this area in China. He described how their progress from sequencing one percent of the human genome to 100 percent of the rice genome. The last talk was by S.K. Brhamachari, the main organizer of the meeting. He recalled his early experimental work pertaining to the hydroxylation of proline, as a graduate student of the MBU. He went on to discuss the major computational genomics and bioinformatics efforts, which are being pursued in conjunction with experimental studies, at his institution in Delhi.

A highlight of the symposium was the participation of the President of India, Abdul Kalam. Kalam made major contributions to Indian space and defense efforts before becoming the president. Kapil Sibal, the new Minister for Science and Technology, discussed the Indian government's commitment to scientific research and promised to remove the bureaucratic bottle necks that can get in the way of its meaningful pursuit. The President also interacted in a question-answer session with students.

Ramachandran's active research career in structural biology ended almost 25 years ago, well before his death in 2001, yet he remains a vibrant presence in the field. He was arguably the most outstanding scientist to have worked in independent India. He demonstrated how international science could be decisively influenced even when working under difficult conditions in less well-endowed neighbourhoods. The August 7 symposium was indeed a fitting tribute to his memory.

M. Vijayan